ORCID Profile
0000-0001-5321-0288
Current Organisation
University College London
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Research Topics
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Neurosciences | Sensory Systems | Physiology | Complex Physical Systems | Decision Making | Sensory Systems | Systems Physiology | Central Nervous System | Peripheral Nervous System | Psychology | Neurobiology | Animal Physiology—Cell | Animal Physiology—Systems | Central Nervous System | Diagnostic Applications | Sensory Processes, Perception and Performance | Intelligent Robotics
ANZSRC Socio-Economic Objective (SEO)
Hearing, vision, speech and their disorders | Nervous system and disorders | Health related to ageing | Expanding Knowledge in Psychology and Cognitive Sciences | Medical instrumentation | Behavioural and cognitive sciences | Expanding Knowledge in the Physical Sciences | Expanding Knowledge in the Biological Sciences | Organs, diseases and abnormal conditions not elsewhere classified |
Related Links
Publications
Multimodal optogenetic neural interfacing device fabricated by scalable optical fiber drawing technique
Publisher: The Optical Society
Date: 25-11-2015
DOI: 10.1364/AO.54.010068
Retinal ganglion cells and the magnocellular, parvocellular, and koniocellular subcortical visual pathways from the eye to the brain
Publisher: Elsevier
Date: 2021
fMRI adaptation revisited
Publisher: Elsevier BV
Date: 07-2016
Disrupted visual cortical plasticity in early neurodegeneration
Publisher: Cold Spring Harbor Laboratory
Date: 04-11-2020
DOI: 10.1101/2020.11.02.365767
Abstract: Neurodegeneration is a hallmark of many dementias and is thought to underlie a progressive impairment of neural plasticity. How neurodegeneration affects plasticity in neural circuits is not known. We therefore characterised the impact of tau-driven neurodegeneration on plasticity in the visual system, where normal function is well understood. We studied a very simple form of visual plasticity that allowed us to track both long timescales (across days) and shorter timescales (over minutes). We recorded the local field potential in the primary visual cortex of rTg4510 transgenic mice, a mouse model of tauopathy, while animals were repeatedly exposed to the same stimulus over the course of 9 days. We studied animals at early stages of neurodegeneration (5 months old) and at a more advanced stage where pathology is evident (8 months). We found that both short- and long-term visual plasticity were already disrupted at early stages of neurodegeneration, and were further reduced in older animals, such that it was abolished in mice expressing the mutant tau. Additionally, we found that visually evoked behaviours were disrupted in both younger and older mice expressing the mutant tau. Our results show that visual cortical plasticity and visually evoked behaviours are disrupted in the rTg4510 model of tauopathy, even at early stages of neurodegeneration. This simple measure of neural plasticity may help understand how neurodegeneration disrupts neural circuits, and offers a translatable platform for detection and tracking of the disease. Visual plasticity is disrupted at early stages of neurodegeneration in rTg4510 mice Visual plasticity is reduced in older animals, particularly during neurodegeneration Instinctive visual behaviours are reduced in neurodegeneration Short-term visual plasticity is reduced in neurodegeneration
Spectral Signatures of Feedforward and Recurrent Circuitry in Monkey Area MT
Publisher: Oxford University Press (OUP)
Date: 10-05-2016
Abstract: Recordings of local field potential (LFP) in the visual cortex can show rhythmic activity at gamma frequencies (30-100 Hz). While the gamma rhythms in the primary visual cortex have been well studied, the structural and functional characteristics of gamma rhythms in extrastriate visual cortex are less clear. Here, we studied the spatial distribution and functional specificity of gamma rhythms in extrastriate middle temporal (MT) area of visual cortex in marmoset monkeys. We found that moving gratings induced narrowband gamma rhythms across cortical layers that were coherent across much of area MT. Moving dot fields instead induced a broadband increase in LFP in middle and upper layers, with weaker narrowband gamma rhythms in deeper layers. The stimulus dependence of LFP response in middle and upper layers of area MT appears to reflect the presence (gratings) or absence (dot fields and other textures) of strongly oriented contours. Our results suggest that gamma rhythms in these layers are propagated from earlier visual cortex, while those in the deeper layers may emerge in area MT.
Temporal response properties of koniocellular (blue-on and blue-off) cells in marmoset lateral geniculate nucleus
Publisher: American Physiological Society
Date: 15-09-0066
Abstract: Visual perception requires integrating signals arriving at different times from parallel visual streams. For ex le, signals carried on the phasic-magnocellular (MC) pathway reach the cerebral cortex pathways some tens of milliseconds before signals traveling on the tonic-parvocellular (PC) pathway. Visual latencies of cells in the koniocellular (KC) pathway have not been specifically studied in simian primates. Here we compared MC and PC cells to “blue-on” (BON) and “blue-off” (BOF) KC cells these cells carry visual signals originating in short-wavelength-sensitive (S) cones. We made extracellular recordings in the lateral geniculate nucleus (LGN) of anesthetized marmosets. We found that BON visual latencies are 10–20 ms longer than those of PC or MC cells. A small number of recorded BOF cells ( n = 7) had latencies 10–20 ms longer than those of BON cells. Within all cell groups, latencies of foveal receptive fields ( ° eccentricity) were longer (by 3–8 ms) than latencies of peripheral receptive fields ( °). Latencies of yellow-off inputs to BON cells lagged the blue-on inputs by up to 30 ms, but no differences in visual latency were seen on comparing marmosets expressing dichromatic (“red-green color-blind”) or trichromatic color vision phenotype. We conclude that S-cone signals leaving the LGN on KC pathways are delayed with respect to signals traveling on PC and MC pathways. Cortical circuits serving color vision must therefore integrate across delays in (red-green) chromatic signals carried by PC cells and (blue-yellow) signals carried by KC cells.
Interactions between color and luminance in the perception of orientation
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 25-02-2003
DOI: 10.1167/3.2.1
Two expressions of surround suppression in V1 that arise independent of cortical mechanisms of suppression
Publisher: Cambridge University Press (CUP)
Date: 2007
DOI: 10.1017/S0952523807070022
Abstract: The preferred stimulus size of a V1 neuron decreases with increases in stimulus contrast. It has been supposed that stimulus contrast is the primary determinant of such spatial summation in V1 cells, though the extent to which it depends on other stimulus attributes such as orientation and spatial frequency remains untested. We investigated this by recording from single cells in V1 of anaesthetized cats and monkeys, measuring size-tuning curves for high-contrast drifting gratings of optimal spatial configuration, and comparing these curves with those obtained at lower contrast or at sub-optimal orientations or spatial frequencies. For drifting gratings of optimal spatial configuration, lower contrasts produced less surround suppression resulting in increases in preferred size. High contrast gratings of sub-optimal spatial configuration produced more surround suppression than optimal low-contrast gratings, and as much or more surround suppression than optimal high-contrast gratings. For sub-optimal spatial frequencies, preferred size was similar to that for the optimal high-contrast stimulus, whereas for sub-optimal orientations, preferred size was smaller than that for the optimal high-contrast stimulus. These results indicate that, while contrast is an important determinant of spatial summation in V1, it is not the only determinant. Simulation of these experiments on a cortical receptive field modeled as a Gabor revealed that the small preferred sizes observed for non-preferred stimuli could result simply from linear filtering by the classical receptive field. Further simulations show that surround suppression in retinal ganglion cells and LGN cells can be propagated to neurons in V1, though certain properties of the surround seen in cortex indicate that it is not solely inherited from earlier stages of processing.
Cortical-Like Receptive Fields in the Lateral Geniculate Nucleus of Marmoset Monkeys
Publisher: Society for Neuroscience
Date: 17-04-2013
DOI: 10.1523/JNEUROSCI.5208-12.2013
Abstract: Most neurons in primary visual cortex (V1) exhibit high selectivity for the orientation of visual stimuli. In contrast, neurons in the main thalamic input to V1, the lateral geniculate nucleus (LGN), are considered to be only weakly orientation selective. Here we characterize a sparse population of cells in marmoset LGN that show orientation and spatial frequency selectivity as great as that of cells in V1. The recording position in LGN and histological reconstruction of these cells shows that they are part of the koniocellular (K) pathways. Accordingly we have named them K-o (“koniocellular-orientation”) cells. Most K-o cells prefer vertically oriented gratings their contrast sensitivity and TF tuning are similar to those of parvocellular cells, and they receive negligible functional input from short wavelength-sensitive (“blue”) cone photoreceptors. Four K-o cells tested displayed binocular responses. Our results provide further evidence that in primates as in nonprimate mammals the cortical input streams include a ersity of visual representations. The presence of K-o cells increases functional homologies between K pathways in primates and “sluggish/W” pathways in nonprimate visual systems.
Chromatic tuning of binocular neurons in early visual cortex
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 16-03-2010
DOI: 10.1167/3.9.24
Brief stimuli cast a persistent long-term trace in visual cortex
Publisher: Cold Spring Harbor Laboratory
Date: 10-02-2021
DOI: 10.1101/2021.02.10.430579
Abstract: Visual processing is strongly influenced by the recent stimulus history – a phenomenon termed adaptation. Prominent theories cast adaptation as a consequence of optimized encoding of visual information, by exploiting the temporal statistics of the world. However, this would require the visual system to track the history of in idual briefly experienced events, within a stream of visual input, to build up statistical representations over longer timescales. Here, using an openly available dataset from the Allen Brain Observatory, we show that neurons in the early visual cortex of the mouse indeed maintain long-term traces of in idual past stimuli that persist despite the presentation of several intervening stimuli, leading to long-term and stimulus-specific adaptation over dozens of seconds. Long-term adaptation was selectively expressed in cortical, but not in thalamic neurons, which only showed short-term adaptation. Early visual cortex thus maintains concurrent stimulusspecific memory traces of past input, enabling the visual system to build up a statistical representation of the world to optimize the encoding of new information in a changing environment. In the natural world, previous sensory input is predictive of current input over multi-second timescales. The visual system could exploit these predictabilities by adapting current visual processing to the long-term history of visual input. However, it is unclear whether the visual system can track the history of in idual briefly experienced images, within a stream of input, to build up statistical representations over such long timescales. Here, we show that neurons in early visual cortex of the mouse brain exhibit remarkably long-term adaptation to brief stimuli, persisting over dozens of seconds, and despite the presentation of several intervening stimuli. The visual cortex thus maintains long-term traces of in idual briefly experienced past images, enabling the formation of statistical representations over extended timescales.
Habituation Reveals Fundamental Chromatic Mechanisms in Striate Cortex of Macaque
Publisher: Society for Neuroscience
Date: 30-01-2008
DOI: 10.1523/JNEUROSCI.4682-07.2008
Abstract: Prolonged viewing of a chromatically modulated stimulus usually leads to changes in its appearance, and that of similar stimuli. These aftereffects of habituation have been thought to reflect the activity of two populations of neurons in visual cortex that have particular importance in color vision, one sensitive to red–green modulation, the other to blue–yellow, but they have not been identified. We show here, in recordings from macaque primary visual cortex (V1), that prolonged exposure to chromatic modulation reveals two fundamental mechanisms with distinctive chromatic signatures that match those of the mechanisms identified by perceptual observations. In nearly all neurons, these mechanisms contribute to both excitation and to regulatory gain controls, and as a result their habituation can have paradoxical effects on response. The mechanisms must be located near the input layers of V1, before their distinct chromatic signatures diffuse. Our observations suggest that the fundamental mechanisms do not give rise to two distinct L–M and S chromatic pathways. Rather, the mechanisms are better understood as stages in the elaboration of chromatic tuning, expressed in varying proportions in all cells in V1 (and beyond), and made accessible to physiological and perceptual investigation only through habituation.
A simpler primate brain: the visual system of the marmoset monkey
Publisher: Frontiers Media SA
Date: 08-08-2014
iPSC‐derived human cardiac progenitor cells improve ventricular remodelling via angiogenesis and interstitial networking of infarcted myocardium
Publisher: Wiley
Date: 27-11-2015
DOI: 10.1111/JCMM.12725
Colour-luminance interactions in human orientation perception
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 15-03-2002
DOI: 10.1167/2.7.215
Functional Organisation of the Mouse Superior Colliculus
Publisher: Frontiers Media SA
Date: 29-04-2022
DOI: 10.3389/FNCIR.2022.792959
Abstract: The superior colliculus (SC) is a highly conserved area of the mammalian midbrain that is widely implicated in the organisation and control of behaviour. SC receives input from a large number of brain areas, and provides outputs to a large number of areas. The convergence and ergence of anatomical connections with different areas and systems provides challenges for understanding how SC contributes to behaviour. Recent work in mouse has provided large anatomical datasets, and a wealth of new data from experiments that identify and manipulate different cells within SC, and their inputs and outputs, during simple behaviours. These data offer an opportunity to better understand the roles that SC plays in these behaviours. However, some of the observations appear, at first sight, to be contradictory. Here we review this recent work and hypothesise a simple framework which can capture the observations, that requires only a small change to previous models. Specifically, the functional organisation of SC can be explained by supposing that three largely distinct circuits support three largely distinct classes of simple behaviours–arrest, turning towards, and the triggering of escape or capture. These behaviours are hypothesised to be supported by the optic, intermediate and deep layers, respectively.
Visual Motion Discrimination by Propagating Patterns in Primate Cerebral Cortex
Publisher: Society for Neuroscience
Date: 14-09-2017
DOI: 10.1523/JNEUROSCI.1538-17.2017
Abstract: Visual stimuli can evoke waves of neural activity that propagate across the surface of visual cortical areas. The relevance of these waves for visual processing is unknown. Here, we measured the phase and litude of local field potentials (LFPs) in electrode array recordings from the motion-processing medial temporal (MT) area of anesthetized male marmosets. Animals viewed grating or dot-field stimuli drifting in different directions. We found that, on in idual trials, the direction of LFP wave propagation is sensitive to the direction of stimulus motion. Propagating LFP patterns are also detectable in trial-averaged activity, but the trial-averaged patterns exhibit different dynamics and behaviors from those in single trials and are similar across motion directions. We show that this difference arises because stimulus-sensitive propagating patterns are present in the phase of single-trial oscillations, whereas the trial-averaged signal is dominated by additive litude effects. Our results demonstrate that propagating LFP patterns can represent sensory inputs at timescales relevant to visually guided behaviors and raise the possibility that propagating activity patterns serve neural information processing in area MT and other cortical areas. SIGNIFICANCE STATEMENT Propagating wave patterns are widely observed in the cortex, but their functional relevance remains unknown. We show here that visual stimuli generate propagating wave patterns in local field potentials (LFPs) in a movement-sensitive area of the primate cortex and that the propagation direction of these patterns is sensitive to stimulus motion direction. We also show that averaging LFP signals across multiple stimulus presentations (trial averaging) yields propagating patterns that capture different dynamic properties of the LFP response and show negligible direction sensitivity. Our results demonstrate that sensory stimuli can modulate propagating wave patterns reliably in the cortex. The relevant dynamics are normally masked by trial averaging, which is a conventional step in LFP signal processing.
Brief Stimuli Cast a Persistent Long-Term Trace in Visual Cortex
Publisher: Society for Neuroscience
Date: 21-01-2022
DOI: 10.1523/JNEUROSCI.1350-21.2021
Abstract: Visual processing is strongly influenced by recent stimulus history, a phenomenon termed adaptation. Prominent theories cast adaptation as a consequence of optimized encoding of visual information by exploiting the temporal statistics of the world. However, this would require the visual system to track the history of in idual briefly experienced events, within a stream of visual input, to build up statistical representations over longer timescales. Here, using an openly available dataset from the Allen Brain Observatory, we show that neurons in the early visual cortex of the mouse indeed maintain long-term traces of in idual past stimuli that persist despite the presentation of several intervening stimuli, leading to long-term and stimulus-specific adaptation over dozens of seconds. Long-term adaptation was selectively expressed in cortical, but not in thalamic, neurons, which only showed short-term adaptation. Early visual cortex thus maintains concurrent stimulus-specific memory traces of past input, enabling the visual system to build up a statistical representation of the world to optimize the encoding of new information in a changing environment. SIGNIFICANCE STATEMENT In the natural world, previous sensory input is predictive of current input over multisecond timescales. The visual system could exploit these predictabilities by adapting current visual processing to the long-term history of visual input. However, it is unclear whether the visual system can track the history of in idual briefly experienced images, within a stream of input, to build up statistical representations over such long timescales. Here, we show that neurons in early visual cortex of the mouse brain exhibit remarkably long-term adaptation to brief stimuli, persisting over dozens of seconds, and despite the presentation of several intervening stimuli. The visual cortex thus maintains long-term traces of in idual briefly experienced past images, enabling the formation of statistical representations over extended timescales.
Colour and pattern selectivity of receptive fields in superior colliculus of marmoset monkeys
Publisher: Wiley
Date: 27-07-2012
Centre-surround effects on perceived orientation in complex images
Publisher: Elsevier BV
Date: 06-2008
DOI: 10.1016/J.VISRES.2008.02.023
Abstract: Using the simultaneous tilt illusion [Gibson, J., & Radner, M. (1937). Adaptation, after-effect and contrast in the perception of tilted lines. Journal of Experimental Psychology, 12, 453-467], we investigate the perception of orientation in natural images and textures with similar statistical properties. We show that the illusion increases if observers judge the average orientation of textures rather than sinusoidal gratings. Furthermore, the illusion can be induced by surrounding textures with a broad range of orientations, even those without a clearly perceivable orientation. A robust illusion is induced by natural images, and is increased by randomising the phase spectra of those images. We present a simple model of orientation processing that can accommodate most of our observations.
Molecular pathogenesis of Marfan syndrome
Publisher: Elsevier BV
Date: 05-2015
DOI: 10.1016/J.IJCARD.2015.03.423
Abstract: Marfan syndrome (MFS) is a genetic disorder that affects multiple organs. Mortality imposed by aortic aneurysm and dissections represent the most serious clinical manifestation of MFS. Progressive pathological aortic root enlargement as the result of degeneration of microfibril architecture and consequential loss of extracellular matrix integrity due to fibrillin-1 (FBN1) mutations are commonly diagnosed clinical manifestations of MFS. However, overlapping clinical manifestations with other aneurysmal disorders present a significant challenge in early and accurate diagnosis of MFS. While FBN1 mutations, abnormal transforming growth factor-β signaling and dysregulated matrix metalloproteinases have been implicated in MFS, clinically accepted risk-stratifying biomarkers have yet to be reliably identified. In this review, we summarize current consensus and recent insights in the understanding of MFS pathogenesis. Finally, we introduce the application of induced pluripotent stem cells (iPSCs) as cellular models for MFS and its potential as a novel platform into providing better appreciation of mechanisms underlying MFS erse manifestations in the cardiovascular system.
Modulation sensitivity of ganglion cells in peripheral retina of macaque
Publisher: Elsevier BV
Date: 12-2002
DOI: 10.1016/S0042-6989(02)00414-5
Abstract: There is le psychophysical evidence that flicker is more salient in the peripheral than the central visual field, but the physiological basis of this eccentricity-dependant change is unclear. Here, we compared responsivity to temporal modulation of ganglion cells in central and peripheral primate retina. Above 30 Hz modulation frequency, both magnocellular (MC) and parvocellular (PC) pathway cells are more responsive in peripheral retina. This suggests that an increase in high-frequency temporal responsiveness arises in outer retina before the MC and PC pathways erge. In both central and peripheral retina, the critical fusion frequency of MC cells is higher than that of PC cells. This result is consistent with other evidence that psychophysical flicker sensitivity is mediated by the MC pathway.
Fractal spike dynamics and neuronal coupling in the primate visual system
Publisher: Wiley
Date: 23-02-2020
DOI: 10.1113/JP278935
Abstract: We measured fractal (self‐similar) fluctuations in ongoing spiking activity in subcortical (lateral geniculate nucleus, LGN) and cortical (area MT) visual areas in anaesthetised marmosets. Cells in the evolutionary ancient koniocellular LGN pathway and in area MT show high‐ litude fractal fluctuations, whereas evolutionarily newer parvocellular and magnocellular LGN cells do not. Spiking activity in koniocellular cells and MT cells shows substantial correlation to the local population activity, whereas activity in parvocellular and magnocellular cells is less correlated with local activity. We develop a model consisting of a fractal process and a global rate modulation which can reproduce and explain the fundamental relationship between fractal fluctuations and population coupling in LGN and MT. The model provides a unified account of apparently disparate aspects of neural spiking activity and can improve our understanding of information processing in evolutionary ancient and modern visual pathways. The brain represents and processes information through patterns of spiking activity, which is influenced by local and widescale brain circuits as well as intrinsic neural dynamics. Whether these influences have independent or linked effects on spiking activity is, however, not known. Here we measured spiking activity in two visual centres, the lateral geniculate nucleus (LGN) and cortical area MT, in marmoset monkeys. By combining the Fano‐factor time curve, power spectral analysis and rescaled range analysis, we reveal inherent fractal fluctuations of spiking activity in LGN and MT. We found that the evolutionary ancient koniocellular (K) pathway in LGN and area MT exhibits strong fractal fluctuations at short ( s) time scales. Parvocellular (P) and magnocellular (M) LGN cells show weaker fractal fluctuations at longer (multi‐second) time scales. In both LGN and MT, the litude and time scale of fractal fluctuations can explain short and long time scale spiking dynamics. We further show differential neuronal coupling of LGN and MT cells to local population spiking activity. The population coupling is intrinsically linked to fractal fluctuations: neurons showing stronger fluctuations are more strongly correlated to the local population activity. To understand this relationship, we modelled spiking activity using a fractal inhomogeneous Poisson process with dynamic rate, which is the product of an intrinsic stochastic fractal rate and a global modulatory gain. Our model explains the intrinsic links between neuronal spike rate and population coupling in LGN and MT, and establishes a unified account of dynamic spiking properties in afferent visual pathways.
BonVision – an open-source software to create and control visual environments
Publisher: Cold Spring Harbor Laboratory
Date: 10-03-2020
DOI: 10.1101/2020.03.09.983775
Abstract: Real-time rendering of closed-loop visual environments is necessary for next-generation understanding of brain function and behaviour, but is prohibitively difficult for non-experts to implement and is limited to few laboratories worldwide. We developed BonVision as an easy-to-use open-source software for the display of virtual or augmented reality, as well as standard visual stimuli. As the architecture is based on the open-source Bonsai graphical programming language, BonVision benefits from native integration with experimental hardware. BonVision therefore enables easy implementation of closed-loop experiments, including real-time interaction with deep neural networks and communication with behavioural and physiological measurement and manipulation devices.
Combination of subcortical color channels in human visual cortex
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 05-2010
DOI: 10.1167/10.5.25
Abstract: Mechanisms of color vision in cortex have not been as well characterized as those in sub-cortical areas, particularly in humans. We used fMRI in conjunction with univariate and multivariate (pattern) analysis to test for the initial transformation of sub-cortical inputs by human visual cortex. Subjects viewed each of two patterns modulating in color between orange-cyan or lime-magenta. We tested for higher order cortical representations of color capable of discriminating these stimuli, which were designed so that they could not be distinguished by the postulated L-M and S-(L + M) sub-cortical opponent channels. We found differences both in the average response and in the pattern of activity evoked by these two types of stimuli, across a range of early visual areas. This result implies that sub-cortical chromatic channels are recombined early in cortical processing to form novel representations of color. Our results also suggest a cortical bias for lime-magenta over orange-cyan stimuli, when they are matched for cone contrast and the response they would elicit in the L-M and S-(L + M) opponent channels.
Special issue: Calibrating the visual system
Publisher: Elsevier BV
Date: 12-2022
Interpreting the dimensions of neural feature representations revealed by dimensionality reduction
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.NEUROIMAGE.2017.06.068
Abstract: Recent progress in understanding the structure of neural representations in the cerebral cortex has centred around the application of multivariate classification analyses to measurements of brain activity. These analyses have proved a sensitive test of whether given brain regions provide information about specific perceptual or cognitive processes. An exciting extension of this approach is to infer the structure of this information, thereby drawing conclusions about the underlying neural representational space. These approaches rely on exploratory data-driven dimensionality reduction to extract the natural dimensions of neural spaces, including natural visual object and scene representations, semantic and conceptual knowledge, and working memory. However, the efficacy of these exploratory methods is unknown, because they have only been applied to representations in brain areas for which we have little or no secondary knowledge. One of the best-understood areas of the cerebral cortex is area MT of primate visual cortex, which is known to be important in motion analysis. To assess the effectiveness of dimensionality reduction for recovering neural representational space we applied several dimensionality reduction methods to multielectrode measurements of spiking activity obtained from area MT of marmoset monkeys, made while systematically varying the motion direction and speed of moving stimuli. Despite robust tuning at in idual electrodes, and high classifier performance, dimensionality reduction rarely revealed dimensions for direction and speed. We use this ex le to illustrate important limitations of these analyses, and suggest a framework for how to best apply such methods to data where the structure of the neural representation is unknown.
Calibrating vision: Concepts and questions
Publisher: Elsevier BV
Date: 12-2022
Re-trafficking of hERG reverses long QT syndrome 2 phenotype in human iPS-derived cardiomyocytes
Publisher: Oxford University Press (OUP)
Date: 12-03-2014
DOI: 10.1093/CVR/CVU060
Abstract: Long QT syndrome 2 (LQTS2) caused by missense mutations in hERG channel is clinically associated with abnormally prolonged ventricular repolarization and sudden cardiac deaths. Modelling monogenic arrhythmogenic diseases using human-induced pluripotent stem cells (hiPSCs) offers unprecedented mechanistic insights into disease pathogenesis. We utilized LQTS2-hiPSC-derived cardiomyocytes (CMs) to elucidate pathological changes and to demonstrate reversal of LQTS2 phenotype in a therapeutic intervention using a pharmacological agent, (N-[N-(N-acetyl-l-leucyl)-l-leucyl]-l-norleucine) (ALLN). We generated LQTS2-specific CMs (A561V missense mutation in KCNH2) from iPSCs using the virus-free reprogramming method. These CMs recapitulate dysfunction of hERG potassium channel with diminished IKr currents, prolonged repolarization durations, and elevated arrhythmogenesis due to reduced membrane localization of glycosylated/mature hERG. Dysregulated expression of folding chaperones and processing proteasomes coupled with sequestered hERG in the endoplasmic reticulum confirmed trafficking-induced disease manifestation. Treatment with ALLN, not only increased membrane localization of mature hERG but also reduced repolarization, increased IKr currents and reduced arrhythmogenic events. Diverged from biophysical interference of hERG channel, our results show that modulation of chaperone proteins could be therapeutic in LQTS2 treatment. Our in vitro study shows an alternative approach to rescue diseased LQTS2 phenotype via corrective re-trafficking therapy using a small chemical molecule, such as ALLN. This potentially novel approach may have ramifications in other clinically relevant trafficking disorders.
Creating and controlling visual environments using BonVision
Publisher: eLife Sciences Publications, Ltd
Date: 21-04-2021
DOI: 10.7554/ELIFE.65541
Abstract: Real-time rendering of closed-loop visual environments is important for next-generation understanding of brain function and behaviour, but is often prohibitively difficult for non-experts to implement and is limited to few laboratories worldwide. We developed BonVision as an easy-to-use open-source software for the display of virtual or augmented reality, as well as standard visual stimuli. BonVision has been tested on humans and mice, and is capable of supporting new experimental designs in other animal models of vision. As the architecture is based on the open-source Bonsai graphical programming language, BonVision benefits from native integration with experimental hardware. BonVision therefore enables easy implementation of closed-loop experiments, including real-time interaction with deep neural networks, and communication with behavioural and physiological measurement and manipulation devices.
Extraclassical Receptive Field Properties of Parvocellular, Magnocellular, and Koniocellular Cells in the Primate Lateral Geniculate Nucleus
Publisher: Society for Neuroscience
Date: 2002
DOI: 10.1523/JNEUROSCI.22-01-00338.2002
Abstract: Descriptions of receptive fields at subcortical levels of the visual system have mostly considered only the classical receptive field (CRF). A suppressive extraclassical receptive field (ECRF) has been demonstrated in relay cells within the primate lateral geniculate nucleus (LGN), but the quantitative properties and specific influence of the ECRF on the distinct magnocellular (MC), koniocellular (KC), and parvocellular (PC) pathways are not known. Here we quantified the effect of ECRF stimulation on visually responsive cells in the LGN of a diurnal New World primate, the marmoset. We show that for all cells, visually evoked responses are reduced by stimulation of the ECRF. The magnitude of the suppression is greatest for MC cells and smallest for PC cells. The effect of ECRF stimulation on KC cells is variable but always suppressive. We refer to these effects as extraclassical inhibition (ECI). The contrast–response relationship of the ECI parallels that of CRF-induced excitation for each cell class: for MC cells, ECI contrast threshold is close to 10% and the ECI saturates at 50% contrast, but the contrast dependence of ECI on PC cells is more linear. The ECI also contributes to contrast-dependent changes in spatial summation: on average for all LGN cells the radius of the excitatory spatial summation field (measured from aperture-tuning curves) at low contrast is 1.31 times that at high contrast. No consistent effects of orientation on ECI were seen. The data suggest that the suppressive component of the ECRF seen in cortical neurons could primarily be inherited from subcortical input streams.
Spatial precision of population activity in primate area MT
Publisher: American Physiological Society
Date: 08-2015
Abstract: The middle temporal (MT) area is a cortical area integral to the “where” pathway of primate visual processing, signaling the movement and position of objects in the visual world. The receptive field of a single MT neuron is sensitive to the direction of object motion but is too large to signal precise spatial position. Here, we asked if the activity of MT neurons could be combined to support the high spatial precision required in the where pathway. With the use of multielectrode arrays, we recorded simultaneously neural activity at 24–65 sites in area MT of anesthetized marmoset monkeys. We found that although in idual receptive fields span more than 5° of the visual field, the combined population response can support fine spatial discriminations ( .2°). This is because receptive fields at neighboring sites overlapped substantially, and changes in spatial position are therefore projected onto neural activity in a large ensemble of neurons. This fine spatial discrimination is supported primarily by neurons with receptive fields flanking the target locations. Population performance is degraded (by 13–22%) when correlations in neural activity are ignored, further reflecting the contribution of population neural interactions. Our results show that population signals can provide high spatial precision despite large receptive fields, allowing area MT to represent both the motion and the position of objects in the visual world.
Altered low-frequency brain rhythms precede changes in gamma power during tauopathy
Publisher: Elsevier BV
Date: 10-2022
Acetylated Signal Transducer and Activator of Transcription 3 Functions as Molecular Adaptor Independent of Transcriptional Activity During Human Cardiogenesis
Publisher: Oxford University Press (OUP)
Date: 31-07-2017
DOI: 10.1002/STEM.2665
Abstract: Activation of signal transducer and activator of transcription 3 (STAT3) is imperative for mammalian development, specifically cardiogenesis. STAT3 phosphorylation and acetylation are key post-translational modifications that regulate its transcriptional activity. Significance of such modifications during human cardiogenesis remains elusive. Using human pluripotent stem cells to recapitulate cardiogenesis, two independently modified STAT3α (92 kDa) isoforms (phosphorylated and acetylated), which perform ergent functions were identified during cardiomyocyte (CM) formation. Phosphorylated STAT3α functioned as the canonical transcriptional activator, while acetylated STAT3α underwent caspase-3-mediated cleavage to generate a novel STAT3ζ fragment (∼45 kDa), which acted as a molecular adaptor integral to the ErbB4-p38γ signaling cascade in driving CM formation. While STAT3α knockdown perturbed cardiogenesis by eliminating both post-translationally modified STAT3α isoforms, caspase-3 knockdown specifically abrogates the function of acetylated STAT3α, resulting in limited STAT3ζ formation thereby preventing nuclear translocation of key cardiac transcription factor Nkx2-5 that disrupted CM formation. Our findings show the coexistence of two post-translationally modified STAT3α isoforms with distinct functions and define a new role for STAT3 as a molecular adaptor that functions independently of its canonical transcriptional activity during human cardiogenesis.
The impact of brief exposure to high contrast on the contrast response of neurons in primate lateral geniculate nucleus
Publisher: American Physiological Society
Date: 09-2011
Abstract: Prolonged exposure to an effective stimulus generally reduces the sensitivity of neurons early in the visual pathway. Yet eye and head movements bring about frequent changes in the retinal image, and it is less clear that exposure to brief presentations will produce similar desensitization. To address this, we made extracellular recordings from single neurons in the lateral geniculate nucleus of anesthetized marmosets, a New World primate. We measured the contrast response for drifting gratings before and after 0.5-s exposure to a high-contrast drifting grating, a stationary grating, or a blank screen. Prior exposure to the drifting grating reduced the contrast sensitivity of cells in the magnocellular pathway, on average by 23% this reduction remained strong when the adapting and test stimuli were separated by 0.4 s. Exposure to a stationary grating of the preferred spatial phase did not change the contrast response exposure to the opposite spatial phase did. None of the brief adaptors reduced the sensitivity of parvocellular cells. We conclude that brief periods of high contrast, such as those that would be expected to occur during a normal visual fixation, are sufficient to reduce the sensitivity of magnocellular-pathway cells.
A New Code for Contrast in the Primate Visual Pathway
Publisher: Society for Neuroscience
Date: 04-04-2007
DOI: 10.1523/JNEUROSCI.5343-06.2007
Abstract: We characterize a hitherto undocumented type of neuron present in the regions bordering the principal layers of the macaque lateral geniculate nucleus. Neurons of this type were distinguished by a high and unusually regular maintained discharge that was suppressed by spatiotemporal modulation of luminance or chromaticity within the receptive field. The response to any effective stimulus was a reduction in discharge, reminiscent of the “suppressed-by-contrast” cells of the cat retina. To a counterphase-modulated grating, the response was a phase-insensitive suppression modulated at twice the stimulus frequency, implying a receptive field comprised of multiple mechanisms that generate rectifying responses. This distinctive nonlinearity makes the neurons well suited to computing a measure of contrast energy such a signal might be important in regulating sensitivity early in visual cortex.
Slow intrinsic rhythm in the koniocellular visual pathway
Publisher: Proceedings of the National Academy of Sciences
Date: 15-08-2011
Abstract: Slow rhythmic changes in nerve-cell activity are characteristic of unconscious brain states and also may contribute to waking brain function by coordinating activity between cortical and subcortical structures. Here we show that slow rhythms are exhibited by the koniocellular (K) pathway, one of three visual pathways beginning in the eye and projecting through the lateral geniculate visual relay nucleus to the cerebral cortex. We recorded activity in pairs and ensembles of neurons in the lateral geniculate nucleus of anesthetized marmoset monkeys. We found slow rhythms are common in K cells but are rare in parvocellular and magnocellular cell pairs. The time course of slow K rhythms corresponds to subbeta ( Hz) EEG frequencies, and high spike rates in K cells are associated with low power in the theta and delta EEG bands. By contrast, spontaneous activity in the parvocellular and magnocellular pathways is neither synchronized nor strongly linked to EEG state. These observations suggest that parallel visual pathways not only carry different kinds of visual signals but also contribute differentially to brain circuits at the first synapse in the thalamus. Differential contribution of sensory streams to rhythmic brain circuits also raises the possibility that sensory stimuli can be tailored to modify brain rhythms.
Emergence of Complex Wave Patterns in Primate Cerebral Cortex
Publisher: Society for Neuroscience
Date: 18-03-2015
DOI: 10.1523/JNEUROSCI.4509-14.2015
Abstract: Slow brain rhythms are attributed to near-simultaneous (synchronous) changes in activity in neuron populations in the brain. Because they are slow and widespread, synchronous rhythms have not been considered crucial for information processing in the waking state. Here we adapted methods from turbulence physics to analyze δ-band (1–4 Hz) rhythms in local field potential (LFP) activity, in multielectrode recordings from cerebral cortex in anesthetized marmoset monkeys. We found that synchrony contributes only a small fraction (less than one-fourth) to the local spatiotemporal structure of δ-band signals. Rather, δ-band activity is dominated by propagating plane waves and spatiotemporal structures, which we call complex waves. Complex waves are manifest at submillimeter spatial scales, and millisecond-range temporal scales. We show that complex waves can be characterized by their relation to phase singularities within local nerve cell networks. We validate the biological relevance of complex waves by showing that nerve cell spike rates are higher in presence of complex waves than in the presence of synchrony and that there are nonrandom patterns of evolution from one type of complex wave to another. We conclude that slow brain rhythms predominantly indicate spatiotemporally organized activity in local nerve cell circuits, not synchronous activity within and across brain regions.
The koniocellular whiteboard
Publisher: Wiley
Date: 30-03-2018
DOI: 10.1002/CNE.24426
Abstract: In 1994 Vivien Casagrande published a review paper in which she summarized evidence for a koniocellular pathway to visual cortex. Here we try to explain how that review moved the field forward, and summarize some key unanswered questions about koniocellular pathways.
Spatial properties of koniocellular cells in the lateral geniculate nucleus of the marmoset Callithrix jacchus
Publisher: Wiley
Date: 06-2001
DOI: 10.1111/J.1469-7793.2001.0519A.X
Abstract: 1. The receptive field dimensions, contrast sensitivity and linearity of spatial summation of koniocellular (KC), parvocellular (PC) and magnocellular (MC) cells in the lateral geniculate nucleus (LGN) of 11 adult marmosets were measured using achromatic sinusoidal gratings. 2. The receptive field centre diameter of cells in each (PC, KC and MC) class increases with distance from the fovea. There is substantial overlap in centre size between the three cell classes at any eccentricity, but the PC cells have, on average, the smallest centres and the KC cells have the largest. Some PC and KC cells did not respond at all to the grating stimulus. 3. The contrast sensitivity of the receptive field centre mechanism in KC cells decreases in proportion to the centre area. A similar trend was seen for the surround mechanism. These characteristics are common to PC and MC cells, suggesting that they originate at an early stage of visual processing in the retina. 4. The KC cells showed, in general, lower peak evoked discharge rates than PC or MC cells. The spontaneous discharge rate of KC cells was lower than that of PC cells and similar to that of MC cells. 5. The majority of cells in all isions of the LGN show linear spatial summation. A few cells did show non-linear spatial summation these cells were predominantly located in the MC and ventral KC layers. 6. The ventral KC layers below and between the MC layers contain cells with larger and more transiently responding receptive fields than cells in the more dorsal KC layers. 7. We conclude that many of the contrast-dependent spatial properties of cells in the marmoset LGN are common to PC, MC and KC cells. The main difference between KC cells and the other two classes is that there is more variability in their response properties, and they are less responsive to high spatial frequencies.
ErbB Receptor Tyrosine Kinase: A Molecular Switch Between Cardiac and Neuroectoderm Specification in Human Pluripotent Stem Cells
Publisher: Oxford University Press (OUP)
Date: 27-06-2016
DOI: 10.1002/STEM.2420
Abstract: Mechanisms determining intrinsic differentiation bias inherent to human pluripotent stem cells (hPSCs) toward cardiogenic fate remain elusive. We evaluated the interplay between ErbB4 and Epidemal growth factor receptor (EGFR or ErbB1) in determining cardiac differentiation in vitro as these receptor tyrosine kinases are key to heart and brain development in vivo. Our results demonstrate that during cardiac differentiation, cell fate biases exist in hPSCs due to cardiac/neuroectoderm ergence post cardiac mesoderm stage. Stage-specific up-regulation of EGFR in concert with persistent Wnt3a signaling post cardiac mesoderm favors commitment toward neural progenitor cells (NPCs). Inhibition of EGFR abrogates these effects with enhanced (& twofold) cardiac differentiation efficiencies by increasing proliferation of Nkx2-5 expressing cardiac progenitors while reducing proliferation of Sox2 expressing NPCs. Forced overexpression of ErbB4 rescued cardiac commitment by augmenting Wnt11 signaling. Convergence between EGFR/ErbB4 and canonical/noncanonical Wnt signaling determines cardiogenic fate in hPSCs.
Author response: Creating and controlling visual environments using BonVision
Publisher: eLife Sciences Publications, Ltd
Date: 08-04-2021
Chromatic and spatial properties of parvocellular cells in the lateral geniculate nucleus of the marmoset (Callithrix jacchus)
Publisher: Wiley
Date: 05-2004
The machinery of colour vision
Publisher: Springer Science and Business Media LLC
Date: 04-2007
DOI: 10.1038/NRN2094
Abstract: Some fundamental principles of colour vision, deduced from perceptual studies, have been understood for a long time. Physiological studies have confirmed the existence of three classes of cone photoreceptors, and of colour-opponent neurons that compare the signals from cones, but modern work has drawn attention to unexpected complexities of early organization: the proportions of cones of different types vary widely among in iduals, without great effect on colour vision the arrangement of different types of cones in the mosaic seems to be random, making it hard to optimize the connections to colour-opponent mechanisms and new forms of colour-opponent mechanisms have recently been discovered. At a higher level, in the primary visual cortex, recent studies have revealed a simpler organization than had earlier been supposed, and in some respects have made it easier to reconcile physiological and perceptual findings.
The Lateral Geniculate Nucleus
Publisher: Wiley
Date: 22-04-2005
Identification of a targeted and testable antiarrhythmic therapy for long-QT syndrome type 2 using a patient-specific cellular model
Publisher: Oxford University Press (OUP)
Date: 21-07-2017
Abstract: Loss-of-function mutations in the hERG gene causes long-QT syndrome type 2 (LQT2), a condition associated with reduced IKr current. Four different mutation classes define the molecular mechanisms impairing hERG. Among them, Class 2 mutations determine hERG trafficking defects. Lumacaftor (LUM) is a drug acting on channel trafficking already successfully tested for cystic fibrosis and its safety profile is well known. We hypothesize that LUM might rescue also hERG trafficking defects in LQT2 and exert anti-arrhythmic effects. From five LQT2 patients, we generated lines of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) harbouring Class 1 and 2 mutations. The effects of LUM on corrected field potential durations (cFPD) and calcium-handling irregularities were verified by multi electrode array and by calcium transients imaging, respectively. Molecular analysis was performed to clarify the mechanism of action of LUM on hERG trafficking and calcium handling. Long-QT syndrome type 2 induced pluripotent stem cell-derived cardiomyocytes mimicked the clinical phenotypes and showed both prolonged cFPD (grossly equivalent to the QT interval) and increased arrhythmias. Lumacaftor significantly shortened cFPD in Class 2 iPSC-CMs by correcting the hERG trafficking defect. Furthermore, LUM seemed to act also on calcium handling by reducing RyR2S2808 phosphorylation in both Class 1 and 2 iPSC-CMs. Lumacaftor, a drug already in clinical use, can rescue the pathological phenotype of LQT2 iPSC-CMs, particularly those derived from Class 2 mutated patients. Our results suggest that the use of LUM in LQT2 patients not protected by β-blockers is feasible and may represent a novel therapeutic option.
Binocular Visual Responses in the Primate Lateral Geniculate Nucleus
Publisher: Elsevier BV
Date: 12-2015
DOI: 10.1016/J.CUB.2015.10.033
Abstract: The dorsal lateral geniculate nucleus (dLGN) in carnivores and primates is a laminated structure, where each layer gets visual input from only one eye [1, 2]. By contrast, in rodents such as mice and rats, the dLGN is not overtly laminated, the retinal terminals from the two eyes are only partially segregated [3, 4], and many cells in the binocular segment of dLGN get excitatory inputs from both eyes [5, 6]. Here, we show that the evolutionary ancient koniocellular (K) ision of primate dLGN, like rodent dLGN, forms a subcortical site of binocular integration. We recorded single-cell activity in dLGN of anesthetized marmoset monkeys. As expected, cells in the parvocellular (P) and magnocellular (M) layers received monocular excitatory inputs. By contrast, many cells in the K layers received excitatory inputs from both eyes. The specialized properties of distinct K sub-populations (for ex le, blue-yellow color selectivity) were preserved across the two eye inputs, and where tested, the contrast sensitivity of each eye input was roughly matched. The results argue that evolutionarily widely separated orders such as rodents and primates have a shared strategy of integrating signals from the two eyes in subcortical circuits.
Receptive field asymmetries produce color-dependent direction selectivity in primate lateral geniculate nucleus
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 08-07-2010
DOI: 10.1167/10.8.1
Abstract: Blue-on receptive fields recorded in primate retina and lateral geniculate nucleus are customarily described as showing overlapping blue-on and yellow-off receptive field components. However, the retinal pathways feeding the blue-on and yellow-off subfields arise from spatially discrete receptor populations, and recent studies have given contradictory accounts of receptive field structure of blue-on cells. Here we analyzed responses of blue-on cells to drifting gratings, in single-cell extracellular recordings from the dorsal lateral geniculate nucleus in marmosets. We show that most blue-on cells exhibit selectivity for the drift direction of achromatic gratings. The standard concentric difference-of-Gaussians (DOG) model thus cannot account for responses of these cells. We apply a simple, anatomically plausible, extension of the DOG model. The model incorporates temporally offset elliptical two-dimensional Gaussian subfields. The model can predict color-contingent direction and spatial tuning. Because direction tuning in blue-on cells depends on stimulus chromaticity, spatial frequency, and temporal frequency, this property is of little value as a general mechanism for image movement detection. It is possible that anatomical wiring for color selectivity has constrained the capacity of blue-on cells to contribute to spatial and motion vision.
Chromatic Gain Controls in Visual Cortical Neurons
Publisher: Society for Neuroscience
Date: 11-05-2005
DOI: 10.1523/JNEUROSCI.5316-04.2005
Abstract: Although the response of a neuron in the visual cortex generally grows nonlinearly with contrast, the spatial tuning of the cell remains stable. This is thought to reflect the activity of a contrast gain control (“normalization”) that has very broad tuning on the relevant stimulus dimension. Contrast invariant tuning on a particular dimension is probably necessary for reliable representation of stimuli on that dimension. In the lateral geniculate nucleus (LGN), V1, and V2 of anesthetized macaque, we measured chromatic tuning of neurons at several contrasts to characterize the gain controls and identify cells that might be important for representing color. We estimated separately the chromatic signature of the linear receptive field and that of the gain control. In the LGN, we found normalization in magnocellular cells and cells receiving excitatory S-cone input but not in parvocellular cells or those receiving inhibitory S-cone input. We found normalization in all types of cortical neurons. Among cells that preferred achromatic modulation, or modulation along intermediate directions in color space (making them responsive to both achromatic and chromatic stimuli), normalization was driven by mechanisms tuned to a restricted range of directions in color space, close to achromatic. As a result, chromatic tuning varied with contrast. Among the relatively few cells that strongly preferred chromatic modulation, normalization was driven by mechanisms sensitive to modulation along all directions in color space, especially isoluminant. As a result, chromatic tuning changed little with contrast. To the extent that contrast invariant tuning is important in representing chromaticity, relatively few cortical neurons are involved.
Association of Cardiomyopathy With MYBPC3 D389V and MYBPC3Δ25bpIntronic Deletion in South Asian Descendants
Publisher: American Medical Association (AMA)
Date: 06-2018
Altered low frequency brain rhythms precede changes in gamma power during tauopathy
Publisher: Cold Spring Harbor Laboratory
Date: 04-08-2021
DOI: 10.1101/2021.08.03.454865
Abstract: Alzheimer’s disease and other dementias are associated with disruptions of electrophysiological brain activity, including low frequency and gamma rhythms. Many of these dementias are also associated with the malfunction of the membrane associated protein tau. Tauopathy disrupts neuronal function and the stability of synapses and is a key driver of neurodegeneration. Here we ask how brain rhythms are affected by tauopathy, at different stages of its progression. We performed local field potential recordings from visual cortex of rTg4510 and control animals at early stages of neurodegeneration (5 months) and at a more advanced stage where pathology is evident (8 months). We measured brain activity in the presence or absence of external visual stimulation, and while monitoring pupil diameter and locomotion to establish animal behavioural states. At 5 months, before substantial pathology, we found an increase in low frequency rhythms during resting state in tauopathic animals. This was because tauopathic animals entered intermittent periods of increased neural synchronisation, where activity across a wide band of low frequencies was strongly correlated. At 8 months, when the degeneration was more advanced, the increased synchronisation and low frequency power was accompanied by a reduction in power in the gamma range, with erse effects across different components of the gamma rhythm. Our results indicate that slower rhythms are impaired earlier than gamma rhythms in tauopathy, suggesting that electrophysiological measurements can indicate both the presence and progression of tauopathic degeneration.
Information processing in the primate visual system
Publisher: Wiley
Date: 23-12-2010
Spike sorting for large, dense electrode arrays
Publisher: Springer Science and Business Media LLC
Date: 14-03-2016
DOI: 10.1038/NN.4268
Early and Late Mechanisms of Surround Suppression in Striate Cortex of Macaque
Publisher: Society for Neuroscience
Date: 14-04-2188
DOI: 10.1523/JNEUROSCI.3414-05.2005
Abstract: The response of a neuron in striate cortex to an optimally configured visual stimulus is generally reduced when the stimulus is enlarged to encroach on a suppressive region that surrounds its classical receptive field (CRF). To characterize the mechanism that gives rise to this suppression, we measured its spatiotemporal tuning, its susceptibility to contrast adaptation, and its capacity for interocular transfer. Responses to an optimally configured grating confined to the CRF were strongly suppressed by annular surrounding gratings drifting at a wide range of temporal and spatial frequencies (including spatially uniform fields) that extended from well below to well above the range that drives most cortical neurons. Suppression from gratings capable of driving cortical CRFs was profoundly reduced by contrast adaptation and showed substantial interocular transfer. Suppression from stimuli that lay outside the spatiotemporal passband of most cortical CRFs was relatively stronger when the stimulus on the CRF was of low contrast, was generally insusceptible to contrast adaptation, and showed little interocular transfer. Our findings point to the existence of two mechanisms of surround suppression: one that is prominent when high-contrast stimuli drive the CRF, is orientation selective, has relatively sharp spatiotemporal tuning, is binocularly driven, and can be substantially desensitized by adaptation the other is relatively more prominent when low-contrast stimuli drive the CRF, has very broad spatiotemporal tuning, is monocularly driven, and is insusceptible to adaptation. Its character suggests an origin in the input layers of primary visual cortex, or earlier.
Dynamic Contextual Modulation in Superior Colliculus of Awake Mouse
Publisher: Society for Neuroscience
Date: 31-08-2020
DOI: 10.1523/ENEURO.0131-20.2020
Abstract: The responses of neurons in the visual pathway depend on the context in which a stimulus is presented. Responses to predictable stimuli are usually suppressed, highlighting responses to unexpected stimuli that might be important for behavior. Here, we established how context modulates the response of neurons in the superior colliculus (SC), a region important in orienting toward or away from visual stimuli. We made extracellular recordings from single units in the superficial layers of SC in awake mice. We found strong suppression of visual response by spatial context (surround suppression) and temporal context (adaptation). Neurons showing stronger surround suppression also showed stronger adaptation effects. In neurons where it was present, surround suppression was dynamic and was reduced by adaptation. Adaptation’s effects further revealed two components to surround suppression: one component that was weakly tuned for orientation and adaptable, and another component that was more strongly tuned but less adaptable. The selectivity of the tuned component was flexible, such that suppression was stronger when the stimulus over the surround matched that over the receptive field. Our results therefore reveal strong interactions between spatial and temporal context in regulating the flow of signals through mouse SC, and suggest the presence of a subpopulation of neurons that might signal novelty in either space or time.
Chromatic Organization of Ganglion Cell Receptive Fields in the Peripheral Retina
Publisher: Society for Neuroscience
Date: 04-05-2005
DOI: 10.1523/JNEUROSCI.3921-04.2005
Abstract: This study addresses the chromatic properties of receptive fields in the subcortical visual pathway of primates. There is agreement that, in the central visual field, many cells belonging to the parvocellular (PC) ision of the subcortical pathway show red-green opponent responses, that a subgroup of cells belonging to the koniocellular (KC) pathway shows blue-yellow opponent responses, and that magnocellular (MC) pathway cells show only weak signs of chromatic input. However, the chromatic properties of ganglion cells in the peripheral retina are poorly understood. Here, we measured the temporal-chromatic properties of ganglion cells in extracellular in vivo recordings from peripheral macaque retina. We show that the chromatic responsivity of peripheral KC (“blue-on”) and MC cells is very similar to that of their counterparts in the foveal retina. Cone-opponent responses are expressed only at low temporal frequencies ( Hz) in the majority of peripheral PC cells, and some peripheral PC cells show non-opponent response properties. With these exceptions, the chromatic properties of ganglion cells are essentially preserved throughout the first 50° of visual eccentricity. The main change seen in passing from foveal to peripheral retina is that all ganglion cell classes become more responsive to high temporal-frequency modulation.
Distribution of glycine receptor subunits on primate retinal ganglion cells: a quantitative analysis
Publisher: Wiley
Date: 12-2000
Dynamic population codes of multiplexed stimulus features in primate area MT
Publisher: American Physiological Society
Date: 07-2017
Abstract: The middle-temporal area (MT) of primate visual cortex is critical in the analysis of visual motion. Single-unit studies suggest that the response dynamics of neurons within area MT depend on stimulus features, but how these dynamics emerge at the population level, and how feature representations interact, is not clear. Here, we used multivariate classification analysis to study how stimulus features are represented in the spiking activity of populations of neurons in area MT of marmoset monkey. Using representational similarity analysis we distinguished the emerging representations of moving grating and dot field stimuli. We show that representations of stimulus orientation, spatial frequency, and speed are evident near the onset of the population response, while the representation of stimulus direction is slower to emerge and sustained throughout the stimulus-evoked response. We further found a spatiotemporal asymmetry in the emergence of direction representations. Representations for high spatial frequencies and low temporal frequencies are initially orientation dependent, while those for high temporal frequencies and low spatial frequencies are more sensitive to motion direction. Our analyses reveal a complex interplay of feature representations in area MT population response that may explain the stimulus-dependent dynamics of motion vision. NEW & NOTEWORTHY Simultaneous multielectrode recordings can measure population-level codes that previously were only inferred from single-electrode recordings. However, many multielectrode recordings are analyzed using univariate single-electrode analysis approaches, which fail to fully utilize the population-level information. Here, we overcome these limitations by applying multivariate pattern classification analysis and representational similarity analysis to large-scale recordings from middle-temporal area (MT) in marmoset monkeys. Our analyses reveal a dynamic interplay of feature representations in area MT population response.
Fragile Mental Retardation Protein Interacts with the RNA-Binding Protein Caprin1 in Neuronal RiboNucleoProtein Complexes
Publisher: Public Library of Science (PLoS)
Date: 21-06-2012
Lévy walk dynamics explain gamma burst patterns in primate cerebral cortex
Publisher: Springer Science and Business Media LLC
Date: 15-06-2021
DOI: 10.1038/S42003-021-02256-1
Abstract: Lévy walks describe patterns of intermittent motion with variable step sizes. In complex biological systems, Lévy walks (non-Brownian, superdiffusive random walks) are associated with behaviors such as search patterns of animals foraging for food. Here we show that Lévy walks also describe patterns of oscillatory activity in primate cerebral cortex. We used a combination of empirical observation and modeling to investigate high-frequency (gamma band) local field potential activity in visual motion-processing cortical area MT of marmoset monkeys. We found that gamma activity is organized as localized burst patterns that propagate across the cortical surface with Lévy walk dynamics. Lévy walks are fundamentally different from either global synchronization, or regular propagating waves, because they include large steps that enable activity patterns to move rapidly over cortical modules. The presence of Lévy walk dynamics therefore represents a previously undiscovered mode of brain activity, and implies a novel way for the cortex to compute. We apply a biophysically realistic circuit model to explain that the Lévy walk dynamics arise from critical-state transitions between asynchronous and localized propagating wave states, and that these dynamics yield optimal spatial s ling of the cortical sheet. We hypothesise that Lévy walk dynamics could help the cortex to efficiently process variable inputs, and to find links in patterns of activity among sparsely spiking populations of neurons.
Visual response properties of neurons in the superficial layers of the superior colliculus of awake mouse
Publisher: Wiley
Date: 10-11-2018
DOI: 10.1113/JP276964
Striate cortex in dichromatic and trichromatic marmosets: Neurochemical compartmentalization and geniculate input
Publisher: Wiley
Date: 25-07-2002
DOI: 10.1002/CNE.10327
Abstract: The superficial layers of primate striate cortex (V1) contain a regular pattern of dense staining for cytochrome oxidase (CO) reactivity ("blobs") that receive direct input from the koniocellular layers of the lateral geniculate nucleus. It has been suggested that the blob regions are dedicated to processing color information. Here, the neurochemical compartmentalization of blobs and their input from the lateral geniculate nucleus (LGN) was measured in marmosets (Callithrix jacchus) identified as having either dichromatic or trichromatic color vision. In all animals, layer III of V1 showed a patchy distribution of CO. The spatial density of CO blobs (mean, 4.6 blobs/mm(2) range, 3.9-5.5), blob diameter, and the proportion of cortical area within blobs was not significantly different in dichromats and trichromats. The LGN input was studied by injecting retrograde tracer into V1. The koniocellular layers of the LGN contribute 11% of all relay cells, and form the only geniculate input to upper layer III of V1. Only half of all relay cells in the KC layers express calbindin. There is no obvious difference between dichromats and trichromats in the pattern of the geniculate projection to V1. It is concluded that the trichromatic phenotype is not associated with changes in the gross anatomy, neurochemistry, or organization of the geniculate afferents to the superficial layers of V1.
Excitatory and inhibitory contributions to receptive fields of alpha-like retinal ganglion cells in mouse
Publisher: American Physiological Society
Date: 15-09-2013
Abstract: The ON and OFF pathways that emerge at the first synapse in the retina are generally thought to be streamed in parallel to higher visual areas, but recent work shows cross talk at the level of retinal ganglion cells. The ON pathway drives inhibitory inputs onto some OFF ganglion cells, such that these neurons show “push-pull” convergence of OFF-excitation and ON-disinhibition. In this study we measure the spatial receptive field of excitatory and inhibitory inputs to OFF-sustained (OFF-S) retinal ganglion cells of mouse, establish how contrast adaptation modulates excitatory and inhibitory synaptic inputs, and show the pharmacology of the inhibitory inputs. We find that the spatial tuning properties of excitatory and inhibitory inputs are sufficient to determine the spatial profile of the spike output and that high spatial acuity may be particularly reliant on disinhibitory circuits. Contrast adaptation reduced excitation to OFF-S ganglion cells, as expected, and also unmasked an asymmetry in inhibitory inputs: disinhibition at light-off was immune to contrast adaptation, but inhibition at light-on was substantially reduced. In pharmacological experiments we confirm that inhibitory inputs are partly mediated by glycine, but our measurements also suggest a substantial role for GABA. Our observations therefore reveal functional ersity in the inhibitory inputs to OFF ganglion cells and suggest that in addition to enhancing operational range these inputs help shape the spatial receptive fields of ganglion cells.
Temporal contrast sensitivity in the lateral geniculate nucleus of a New World monkey, the marmoset Callithrix jacchus
Publisher: Wiley
Date: 06-1999
DOI: 10.1111/J.1469-7793.1999.0907S.X
Abstract: 1. The temporal contrast sensitivity of koniocellular, parvocellular and magnocellular cells in the lateral geniculate nucleus (LGN) of nine adult marmosets was measured. The receptive fields of the cells were between 0.3 and 70 deg from the fovea. The stimulus was a large spatially uniform field which was modulated in luminance at temporal frequencies between 0.98 and 64 Hz. 2. For each cell group there was a gradual increase in modulation sensitivity, especially for temporal frequencies below 8 Hz, with increasing distance from the fovea. At any given eccentricity, magnocellular cells had the greatest sensitivity. In central visual field, the sensitivity of koniocellular cells lay between that of parvocellular and magnocellular cells. In peripheral visual field (above 10 deg eccentricity) koniocellular and parvocellular cells had similar sensitivity. 3. The contrast sensitivity of each cell class was dependent on the anaesthetic used. Cells from animals anaesthetized with isoflurane were less sensitive than cells from animals anaesthetized with sufentanil. This effect was more marked for temporal frequencies below 4 Hz. 4. These results are incompatible with the notion that the koniocellular pathway is functionally homologous to a sluggish, W-like pathway in other mammals. At least in terms of their temporal transfer properties, many koniocellular cells are more like parvocellular cells.
Suppressive Surrounds and Contrast Gain in Magnocellular-Pathway Retinal Ganglion Cells of Macaque
Publisher: Society for Neuroscience
Date: 23-08-2006
DOI: 10.1523/JNEUROSCI.0821-06.2006
Abstract: The modulation sensitivity of visual neurons can be influenced by remote stimuli which, when presented alone, cause no change in the ongoing discharge rate of the neuron. We show here that the extraclassical surrounds that underlie these effects are present in magnocellular-pathway (MC) but not in parvocellular-pathway (PC) retinal ganglion cells of the macaque. The response of MC cells to drifting gratings and flashing spots was halved by drifting or contrast-reversing gratings surrounding their receptive fields, but PC cell responses were unaffected. The suppression cannot have arisen from the classical receptive field, or been caused by scattered light, because it could be evoked by annuli that themselves caused little or no response from the cell, and is consistent with the action of a isive suppressive mechanism. Suppression in MC cells was broadly tuned for spatial and temporal frequency and greater at high contrast. If perceptual phenomena with similar stimulus contexts, such as the “shift effect” and saccadic suppression, have a retinal component, then they reflect the activity of the MC pathway.
Moving Sensory Adaptation beyond Suppressive Effects in Single Neurons
Publisher: Elsevier BV
Date: 10-2014
Functional Asymmetries in Visual Pathways Carrying S-Cone Signals in Macaque
Publisher: Society for Neuroscience
Date: 09-04-2008
DOI: 10.1523/JNEUROSCI.5338-07.2008
Abstract: In the lateral geniculate nucleus of macaque, we recorded from neurons with substantial input from S-cones and found that, on several important dimensions, the properties of neurons that receive inhibitory input from S-cones (“S−”) are quite unlike those of neurons that receive excitatory input from S-cones (“S+”). First, the organization of chromatic inputs differs substantially: in S+ cells, S-cone signals were usually opposed by those of L- and M-cones in S− cells, signals from L-cones were usually opposed to those of S- and M-cones. Second, to pure S-cone modulation, S+ cells are twice as sensitive as S− cells, but S− cells were much more susceptible to contrast adaptation. Third, in S− cells but not S+ cells, the spatial frequency resolution for achromatic modulation was often greater, the tuning curve and more bandpass, than that for S-cone modulation. Along the dimensions on which we measured, the properties of the S+ cells were relatively tightly clustered, suggesting a homogenous class. Although the chromatic properties of S− cells are heterogeneous, the distribution of their tuning along other stimulus dimensions does not suggest multiple subtypes.
Inner retinal inhibition shapes the receptive field of retinal ganglion cells in primate.
Publisher: Wiley
Date: 23-10-2014
Adaptable mechanisms sensitive to surface color in human vision
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 27-12-2010
DOI: 10.1167/10.9.17
Abstract: "Color constancy" refers to our ability to recognize the color of a surface despite changes in illumination. A range of cues and mechanisms, from receptoral adaptation to higher order cognitive cues, is thought to contribute to our color constancy ability. Here we used psychophysical adaptation to probe for an adaptable representation of surface color. We used stimuli that were matched for cone contrast when averaged over time but were consistent with either a constant scene under changing illumination or a changing scene. The color opponent aftereffect during adaptation to the constant scene was greater than that induced by the changing scene stimulus. Since the stimuli were matched for the responses they would elicit in receptoral mechanisms, the increased aftereffect in the constant scene condition cannot be wholly attributed to adaptation of receptors and neural mechanisms responsive to raw quantal catch. We interpret our result as most parsimoniously explained by the existence of adaptable mechanisms responsive to surface color, most likely located in early visual cortex.
Noise Normalizes Firing Output of Mouse Lateral Geniculate Nucleus Neurons
Publisher: Public Library of Science (PLoS)
Date: 28-02-2013
Fatty acid metabolism driven mitochondrial bioenergetics promotes advanced developmental phenotypes in human induced pluripotent stem cell derived cardiomyocytes
Publisher: Elsevier BV
Date: 12-2018
DOI: 10.1016/J.IJCARD.2018.08.069
Abstract: Preferential utilization of fatty acids for ATP production represents an advanced metabolic phenotype in developing cardiomyocytes. We investigated whether this phenotype could be attained in human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) and assessed its influence on mitochondrial morphology, bioenergetics, respiratory capacity and ultra-structural architecture. Whole-cell proteome analysis of day 14 and day 30-CMs maintained in glucose media revealed a positive influence of extended culture on mitochondria-related processes that primed the day 30-CMs for fatty acid metabolism. Supplementing the day 30-CMs with palmitate/oleate (fatty acids) significantly enhanced mitochondrial remodeling, oxygen consumption rates and ATP production. Metabolomic analysis upon fatty acid supplementation revealed a β-oxidation fueled ATP elevation that coincided with presence of junctional complexes, intercalated discs, t-tubule-like structures and adult isoform of cardiac troponin T. In contrast, glucose-maintained day 30-CMs continued to harbor underdeveloped ultra-structural architecture and more subdued bioenergetics, constrained by suboptimal mitochondria development. The advanced metabolic phenotype of preferential fatty acid utilization was attained in hiPSC-CMs, whereby fatty acid driven β-oxidation sustained cardiac bioenergetics and respiratory capacity resulting in ultra-structural and functional characteristics similar to those of developmentally advanced cardiomyocytes. Better understanding of mitochondrial bioenergetics and ultra-structural adaptation associated with fatty acid metabolism has important implications in the study of cardiac physiology that are associated with late-onset mitochondrial and metabolic adaptations.
Chromatic sensitivity of ganglion cells in the peripheral primate retina
Publisher: Springer Science and Business Media LLC
Date: 04-2001
DOI: 10.1038/35073587
Phasic modulation of Wnt signaling enhances cardiac differentiation in human pluripotent stem cells by recapitulating developmental ontogeny
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1016/J.BBAMCR.2014.06.011
Abstract: Cardiomyocytes (CMs) derived from human pluripotent stem cells (hPSCs) offer immense value in studying cardiovascular regenerative medicine. However, intrinsic biases and differential responsiveness of hPSCs towards cardiac differentiation pose significant technical and logistic hurdles that h er human cardiomyocyte studies. Tandem modulation of canonical and non-canonical Wnt signaling pathways may play a crucial role in cardiac development that can efficiently generate cardiomyocytes from pluripotent stem cells. Our Wnt signaling expression profiles revealed that phasic modulation of canonical/non-canonical axis enabled orderly recapitulation of cardiac developmental ontogeny. Moreover, evaluation of 8 hPSC lines showed marked commitment towards cardiac-mesoderm during the early phase of differentiation, with elevated levels of canonical Wnts (Wnt3 and 3a) and Mesp1. Whereas continued activation of canonical Wnts was counterproductive, its discrete inhibition during the later phase of cardiac differentiation was accompanied by significant up-regulation of non-canonical Wnt expression (Wnt5a and 11) and enhanced Nkx2.5(+) (up to 98%) populations. These Nkx2.5(+) populations transited to contracting cardiac troponin T-positive CMs with up to 80% efficiency. Our results suggest that timely modulation of Wnt pathways would transcend intrinsic differentiation biases of hPSCs to consistently generate functional CMs that could facilitate their scalable production for meaningful clinical translation towards personalized regenerative medicine.
Distribution of calbindin, parvalbumin, and calretinin immunoreactivity in the reticular thalamic nucleus of the marmoset: evidence for a medial leaflet of incertal neurons.
Publisher: Elsevier BV
Date: 08-2000
Relationship between cortical state and spiking activity in the lateral geniculate nucleus of marmosets
Publisher: Wiley
Date: 10-03-2017
DOI: 10.1113/JP273569
Receptive field properties of koniocellular on/off neurons in the lateral geniculate nucleus of marmoset monkeys
Publisher: Society for Neuroscience
Date: 16-10-2018
DOI: 10.1523/JNEUROSCI.1679-18.2018
Abstract: The koniocellular (K) layers of the primate dorsal lateral geniculate nucleus house a variety of visual receptive field types, not all of which have been fully characterized. Here we made single-cell recordings targeted to the K layers of diurnal New World monkeys (marmosets). A subset of recorded cells was excited by both increments and decrements of light intensity (on/off-cells). Histological reconstruction of the location of these cells confirmed that they are segregated to K layers we therefore refer to these cells as K-on/off cells. The K-on/off cells show high contrast sensitivity, strong bandpass spatial frequency tuning, and their response magnitude is strongly reduced by stimuli larger than the excitatory receptive field (silent suppressive surrounds). Stationary counterphase gratings evoke unmodulated spike rate increases or frequency-doubled responses in K-on/off cells such responses are largely independent of grating spatial phase. The K-on/off cells are not orientation or direction selective. Some (but not all) properties of K-on/off cells are consistent with those of local-edge-detector/impressed-by-contrast cells reported in studies of cat retina and geniculate, and broad-thorny ganglion cells recorded in macaque monkey retina. The receptive field properties of K-on/off cells and their preferential location in the ventral K layers (K1 and K2) make them good candidates for the direct projection from geniculate to extrastriate cortical area MT/V5. If so, they could contribute to visual information processing in the dorsal (“where” or “action”) visual stream. SIGNIFICANCE STATEMENT We characterize cells in an evolutionary ancient part of the visual pathway in primates. The cells are located in the lateral geniculate nucleus (the main visual afferent relay nucleus), in regions called koniocellular layers that are known to project to extrastriate visual areas as well as primary visual cortex. The cells show high contrast sensitivity and rapid, transient responses to light onset and offset. Their properties suggest they could contribute to visual processing in the dorsal (“where” or “action”) visual stream.
Vision Guides Selection of Freeze or Flight Defense Strategies in Mice
Publisher: Elsevier BV
Date: 08-2016
DOI: 10.1016/J.CUB.2016.06.006
Abstract: In prey species such as mice, avoidance of predators is key to survival and drives instinctual behaviors like freeze or flight [1, 2]. Sensory signals guide the selection of appropriate behavior [3], and for aerial predators only vision provides useful information. Surprisingly, there is no evidence that vision can guide the selection of escape strategies. Fleeing behavior can be readily triggered by a rapidly looming overhead stimulus [4]. Freezing behavior, however, has previously been induced by real predators or their odors [5]. Here, we discover that a small moving disk, simulating the sweep of a predator cruising overhead, is sufficient to induce freezing response in mice. Looming and sweeping therefore provide visual triggers for opposing flight and freeze behaviors and provide evidence that mice innately make behavioral choices based on vision alone. VIDEO ABSTRACT.
Construction of a vascularized hydrogel for cardiac tissue formation in a porcine model
Publisher: Hindawi Limited
Date: 10-01-2018
DOI: 10.1002/TERM.2634
Abstract: Replacing cardiac tissues lost to myocardial infarction remains a therapeutic goal for regenerative therapy in recovering cardiac function. We assessed the feasibility of constructing a macrosized human cardiac tissue construct using pluripotent stem cell-derived cardiomyocytes or control fibroblasts infused fibrin/collagen hydrogel and performed ectopic implantation in peripheral vascular system of a porcine model for 3 weeks. Finally, an optimized vascularized cardiac construct was explanted and grafted onto porcine myocardium for 2 weeks. Myocardial-grafted human cardiac constructs showed a nascent tissue-like organization with aligned cardiomyocytes within the remodelled collagen matrix. Nevertheless, no significant changes in intraconstruct density of cardiomyocytes were observed in the myocardial-grafted constructs (human embryonic stem cell [hESC]-derived cardiomyocyte [n = 4]: 70.5 ± 22.8 troponin I
Neurokinin-1 receptors and spinal cord control of blood pressure in spontaneously hypertensive rats.
Publisher: Elsevier BV
Date: 1999
DOI: 10.1016/S0006-8993(98)01107-X
Abstract: In this study we examined blood pressure and heart rate responses to intrathecal administration of a synthetic NK1-receptor agonist, H2N-(CH2)4-CO-Phe-Phe-Pro-NmeLeu-Met-NH2 (GR 73,632), in spontaneously hypertensive rats (SHR) and their progenitor strain, the Wistar-Kyoto rat (WKY). Sodium pentobarbitone anaesthetised rats with implanted intrathecal catheters were paralysed (pancuronium dibromide) and artificially ventilated. Injection of GR 73,632 at the T9 spinal level evoked dose-dependent increases in mean arterial pressure (MAP) in WKY and SHR. SHR had a lower MAP response threshold than WKY but increase in response with increasing dose was less in SHR than WKY. Biphasic blood pressure responses at high doses were observed in both strains. Prior administration of the NK1-receptor antagonist (3 aR,7aR)-7,7-diphenyl-2-[1-imino-2(methoxyphenyl)ethyl] perhydroisoindol-4-one (RP 67,580) significantly reduced the pressor response in WKY but not SHR. The depressor response was not attenuated in either strain.
Visual spatial location influences selection of instinctive behaviours in mouse
Publisher: The Royal Society
Date: 04-2023
DOI: 10.1098/RSOS.230034
Abstract: Visual stimuli can elicit instinctive approach and avoidance behaviours. In mouse, vision is known to be important for both avoidance of an overhead threat and approach toward a potential terrestrial prey. The stimuli used to characterize these behaviours, however, vary in both spatial location (overhead or near the ground plane) and visual feature (rapidly expanding disc or slowly moving disc). We therefore asked how mice responded to the same visual features presented in each location. We found that a looming black disc induced escape behaviour when presented overhead or to the side of the animal, but the escapes produced by side-looms were less vigorous and often preceded by freezing behaviour. Similarly, small moving discs induced freezing behaviour when presented overhead or to the side of the animal, but side sweeps also elicited approach behaviours, such that mice explored the area of the arena near where the stimulus had been presented. Our observations therefore show that mice combine cues to the location and features of visual stimuli when selecting among potential behaviours.
Plasticity in visual cortex is disrupted in a mouse model of tauopathy
Publisher: Springer Science and Business Media LLC
Date: 20-01-2022
DOI: 10.1038/S42003-022-03012-9
Abstract: Alzheimer’s disease and other dementias are thought to underlie a progressive impairment of neural plasticity. Previous work in mouse models of Alzheimer’s disease shows pronounced changes in artificially-induced plasticity in hippoc us, perirhinal and prefrontal cortex. However, it is not known how degeneration disrupts intrinsic forms of brain plasticity. Here we characterised the impact of tauopathy on a simple form of intrinsic plasticity in the visual system, which allowed us to track plasticity at both long (days) and short (minutes) timescales. We studied rTg4510 transgenic mice at early stages of tauopathy (5 months) and a more advanced stage (8 months). We recorded local field potentials in the primary visual cortex while animals were repeatedly exposed to a stimulus over 9 days. We found that both short- and long-term visual plasticity were already disrupted at early stages of tauopathy, and further reduced in older animals, such that it was abolished in mice expressing mutant tau. Additionally, visually evoked behaviours were disrupted in both younger and older mice expressing mutant tau. Our results show that visual cortical plasticity and visually evoked behaviours are disrupted in the rTg4510 model of tauopathy. This simple measure of plasticity may help understand how tauopathy disrupts neural circuits, and offers a translatable platform for detection and tracking of the disease.
Phase sensitivities, excitatory summation fields, and silent suppressive receptive fields of single neurons in the parastriate cortex of the cat
Publisher: American Physiological Society
Date: 10-2011
Abstract: We have recorded single-neuron activity from cytoarchitectonic area 18 of anesthetized (0.4–0.7% isoflurane in 65% N 2 O-35% O 2 gaseous mixture) domestic cats. Neurons were identified as simple or complex on the basis of the ratios between the phase-variant (F1) component and the mean firing rate (F0) of spike responses to optimized (orientation, direction, spatial and temporal frequencies, size) high-contrast, luminance-modulated, sine-wave drifting gratings (simple: F1/F0 spike-response ratios 1 complex: F1/F0 spike-response ratios 1). The predominance (∼80%) of simple cells among the neurons recorded from the principal thalamorecipient layers supports the idea that most simple cells in area 18 might constitute a putative early stage in the visual information processing. Apart from the “spike-generating” regions (the classical receptive fields, CRFs), the receptive fields of three-quarters of area 18 neurons contain silent, extraclassical suppressive regions (ECRFs). The spatial extent of summation areas of excitatory responses was negatively correlated with the strength of the ECRF-induced suppression of spike responses. Lowering the stimulus contrast resulted in an expansion of the summation areas of excitatory responses accompanied by a reduction in the strength of the ECRF-induced suppression. The spatial and temporal frequency and orientation tunings of the ECRFs were much broader than those of the CRFs. Hence, the ECRFs of area 18 neurons appear to be largely “inherited” from their dorsal thalamic inputs. In most area 18 cells, costimulation of CRFs and ECRFs resulted in significant increases in F1/F0 spike-response ratios, and thus there was a contextually modulated functional continuum between the simple and complex cells.
A Systemic Evaluation of Cardiac Differentiation from mRNA Reprogrammed Human Induced Pluripotent Stem Cells
Publisher: Public Library of Science (PLoS)
Date: 28-07-2014
Stereo and motion parallax cues in human 3D vision: Can they vanish without a trace?
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 19-12-2006
DOI: 10.1167/6.12.12
fMRI mapping of the visual system in the mouse brain with interleaved snapshot GE-EPI
Publisher: Elsevier BV
Date: 10-2016
Linear and Nonlinear Contributions to the Visual Sensitivity of Neurons in Primate Lateral Geniculate Nucleus
Publisher: American Physiological Society
Date: 10-2010
Abstract: Several parallel pathways convey retinal signals to the visual cortex of primates. The signals of the parvocellular (P) and magnocellular (M) pathways are well characterized the properties of other rarely encountered cell types are distinctive in many ways, but it is not clear that they can provide signals with the same fidelity. Here we study this by characterizing the temporal receptive field of neurons in the lateral geniculate nucleus of anesthetized marmosets. For each neuron, we measured the response to a flickering uniform field, and, from this, estimated the linear and nonlinear receptive fields using spike-triggered average (STA) and spike-triggered covariance (STC) analyses. As expected the response of most P-cells was dominated by the STA, but the response of most M-cells required additional nonlinear components, and these usually acted to suppress cell responses. The STC analysis showed stronger suppressive axes in suppressed-by-contrast cells, and both suppressive and excitatory axes in on-off cells. Together, the STA and the STC analyses form a model of the temporal response to a large uniform field: under this model, the information that was provided by suppressed-by-contrast cells or on-off cells approached that provided by the P- and M-cells. However, whereas P- and M-cells provided more information about luminance, the nonlinear cells provided more information about the contrast energy. This suggests that the nonlinear cells provide complimentary signals to those of P- and M-cells, with reasonably high fidelity, and may play an important role in normal visual processing.
The Impact of Suppressive Surrounds on Chromatic Properties of Cortical Neurons
Publisher: Society for Neuroscience
Date: 07-01-2004
DOI: 10.1523/JNEUROSCI.3036-03.2004
Abstract: Stimulation of the suppressive surround of a cortical neuron affects the responsivity and tuning of the classical receptive field (CRF) on several stimulus dimensions. In V1 and V2 of macaques prepared for acute electrophysiological experiments, we explored the chromatic sensitivity of the surround and its influence on the chromatic tuning of the CRF. We studied receptive fields of single neurons with patches of drifting grating of optimal spatial frequency and orientation and variable size, modulated along achromatic or isoluminant color directions. The responses of most neurons declined as the patch was enlarged beyond the optimal size (surround suppression). In V1 the suppression evoked by isoluminant gratings was less than one-half that evoked by achromatic gratings. Consequently, many cells were most sensitive to achromatic modulation when patches just covered the CRF but were most sensitive to isoluminant modulation when patches were enlarged to cover the suppressive surround. Non-oriented neurons that were strongly chromatically opponent generally lacked suppressive surrounds. In V2 most neurons showed equal surround suppression from isoluminant gratings and achromatic gratings. This makes the relative sensitivity of V2 neurons to achromatic and isoluminant gratings mainly independent of the size of the grating. We also measured the chromatic properties of the CRF in the presence of differently colored surrounds. In neither V1 nor V2 did the surround alter the chromatic tuning of the CRF. Cortical mechanisms sensitive to chromatic contrast seem to provide little input to the suppressive surrounds of V1 neurons but substantial input to those of V2 neurons.
Contrast sensitivity in natural scenes depends on edge as well as spatial frequency structure
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 09-2009
DOI: 10.1167/9.10.1
ErbB4 Activated p38γ MAPK Isoform Mediates Early Cardiogenesis Through NKx2.5 in Human Pluripotent Stem Cells
Publisher: Oxford University Press (OUP)
Date: 15-10-2015
DOI: 10.1002/STEM.2223
Abstract: Activation of ErbB4 receptor signaling is instrumental in heart development, lack of which results in embryonic lethality. However, mechanism governing its intracellular signaling remains elusive. Using human pluripotent stem cells, we show that ErbB4 is critical for cardiogenesis whereby its genetic knockdown results in loss of cardiomyocytes. Phospho-proteome profiling and Western blot studies attribute this loss to inactivation of p38γ MAPK isoform which physically interacts with NKx2.5 and GATA4 transcription factors. Post-cardiomyocyte formation p38γ/NKx2.5 downregulation is followed by p38α/MEF2c upregulation suggesting stage-specific developmental roles of p38 MAPK isoforms. Knockdown of p38γ MAPK similarly disrupts cardiomyocyte formation in spite of the presence of NKx2.5. Cell fractionation and NKx2.5 phosphorylation studies suggest inhibition of ErbB4-p38γ signaling hinders NKx2.5 nuclear translocation during early cardiogenesis. This study reveals a novel pathway that directly links ErbB4 and p38γ to the transcriptional machinery of NKx2.5-GATA4 complex which is critical for cardiomyocyte formation during mammalian heart development.
Color responsiveness argues against a dorsal component of human V4.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 05-04-2011
DOI: 10.1167/11.4.3
Abstract: The retinotopic organization, position, and functional responsiveness of some early visual cortical areas in human and non-human primates are consistent with their being homologous structures. The organization of other areas remains controversial. A critical debate concerns the potential human homologue of macaque area V4, an area very responsive to colored images: specifically, whether human V4 is ided between ventral and dorsal components, as in the macaque, or whether human V4 is confined to one ventral area. We used fMRI to define these areas retinotopically in human and to test the impact of image color on their responsivity. We found a robust preference for full-color movie segments over a luminance-matched achromatic version in ventral V4 but little or no preference in the vicinity of the putative dorsal counterpart. Contrary to previous reports that visual field coverage in the ventral part of V4 is deficient without the dorsal part, we found that coverage in ventral V4 extended to the lower vertical meridian, including the entire contralateral hemifield. Together these results provide evidence against a dorsal component of human V4. Instead, they are consistent with human V4 being a single, ventral region that is sensitive to the chromatic components of images.
Color responsiveness argues against a dorsal component of human V4
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 04-2011
DOI: 10.1167/11.4.1
Abstract: It has long been known that an outward mask is much more disruptive than an inward mask in crowding (H. Bouma, 1973). We show that the locus of attention strongly affects this inward-outward anisotropy, removing it in some conditions and reversing it in others. In a 2AFC paradigm, subjects identified whether a high-contrast Gabor target of a given orientation was presented left or right of fixation. When a fixed eccentricity (8°) was used, the outward plaid mask produced much stronger crowding than the inward mask. When 7°, 8°, and 9° eccentricities were interleaved within the same run, diffusing attention, the inward and outward masks produced the same amount of crowding for all three eccentricities. When target identification was contingent on a foveal cue, biasing attention inward, the inward mask produced stronger crowding. Finally, a new contrast-detection paradigm was used to demonstrate that attention is generally mislocalized outward of the target, which may explain the commonly observed anisotropy in crowding. Our results suggest that spatial attention is intimately involved in the mechanism of crowding.
Temporal Contingencies Determine Whether Adaptation Strengthens or Weakens Normalization
Publisher: Society for Neuroscience
Date: 05-10-2018
DOI: 10.1523/JNEUROSCI.1131-18.2018
Abstract: A fundamental and nearly ubiquitous feature of sensory encoding is that neuronal responses are strongly influenced by recent experience, or adaptation. Theoretical and computational studies have proposed that many adaptation effects may result in part from changes in the strength of normalization signals. Normalization is a “canonical” computation in which a neuron's response is modulated (normalized) by the pooled activity of other neurons. Here, we test whether adaptation can alter the strength of cross-orientation suppression, or masking, a paradigmatic form of normalization evident in primary visual cortex (V1). We made extracellular recordings of V1 neurons in anesthetized male macaques and measured responses to plaid stimuli composed of two overlapping, orthogonal gratings before and after prolonged exposure to two distinct adapters. The first adapter was a plaid consisting of orthogonal gratings and led to stronger masking. The second adapter presented the same orthogonal gratings in an interleaved manner and led to weaker masking. The strength of adaptation's effects on masking depended on the orientation of the test stimuli relative to the orientation of the adapters, but was independent of neuronal orientation preference. Changes in masking could not be explained by altered neuronal responsivity. Our results suggest that normalization signals can be strengthened or weakened by adaptation depending on the temporal contingencies of the adapting stimuli. Our findings reveal an interplay between two widespread computations in cortical circuits, adaptation and normalization, that enables flexible adjustments to the structure of the environment, including the temporal relationships among sensory stimuli. SIGNIFICANCE STATEMENT Two fundamental features of sensory responses are that they are influenced by adaptation and that they are modulated by the activity of other nearby neurons via normalization. Our findings reveal a strong interaction between these two aspects of cortical computation. Specifically, we show that cross-orientation masking, a form of normalization, can be strengthened or weakened by adaptation depending on the temporal contingencies between sensory inputs. Our findings support theoretical proposals that some adaptation effects may involve altered normalization and offer a network-based explanation for how cortex adjusts to current sensory demands.
Profound Contrast Adaptation Early in the Visual Pathway
Publisher: Elsevier BV
Date: 04-2004
DOI: 10.1016/S0896-6273(04)00178-3
Abstract: Prior exposure to a moving grating of high contrast led to a substantial and persistent reduction in the contrast sensitivity of neurons in the lateral geniculate nucleus (LGN) of macaque. This slow contrast adaptation was potent in all magnocellular (M) cells but essentially absent in parvocellular (P) cells and neurons that received input from S cones. Simultaneous recordings of M cells and the potentials of ganglion cells driving them showed that adaptation originated in ganglion cells. As expected from the spatiotemporal tuning of M cells, adaptation was broadly tuned for spatial frequency and lacked orientation selectivity. Adaptation could be induced by high temporal frequencies to which cortical neurons do not respond, but not by low temporal frequencies that can strongly adapt cortical neurons. Our observations confirm that contrast adaptation occurs at multiple levels in the visual system, and they provide a new way to reveal the function and perceptual significance of the M pathway.
Adaptable Mechanisms That Regulate the Contrast Response of Neurons in the Primate Lateral Geniculate Nucleus
Publisher: Society for Neuroscience
Date: 15-04-2009
DOI: 10.1523/JNEUROSCI.0219-09.2009
Abstract: The response of the classical receptive field of visual neurons can be suppressed by stimuli that, when presented alone, cause no change in the discharge rate. This suppression reveals the presence of an extraclassical receptive field (ECRF). In recordings from the lateral geniculate nucleus (LGN) of a New World primate, the marmoset, we characterize the mechanisms that contribute to the ECRF by measuring their spatiotemporal tuning during prolonged exposure to a high-contrast grating (contrast adaptation). The ECRF was strongest in magnocellular cells, where contrast adaptation reduced suppression from the ECRF: adaptation of the ECRF transferred across spatial frequency, temporal frequency, and orientation, but not across space. This implies that the ECRF of LGN cells comprises multiple adaptable mechanisms, each broadly tuned but spatially localized, and consistent with a retinal origin. Signals from the ECRF saturated at high contrasts, and so adaptation of one part of the ECRF brought into its operating range signals from other parts of the visual field. Although the ECRF is adaptable, its major impact during contrast adaptation to a spatially extended pattern was to reduce visual response and hence reduce a neuron's susceptibility to contrast adaptation in normal viewing, a major role of the ECRF might be to protect visual sensitivity in scenes dominated by high contrast.
Cortical representation of color is binocular
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 11-03-2008
DOI: 10.1167/8.3.6
Chromatic summation and receptive field properties of blue-on and blue-off cells in marmoset lateral geniculate nucleus
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.VISRES.2017.09.002
Abstract: The "blue-on" and "blue-off" receptive fields in retina and dorsal lateral geniculate nucleus (LGN) of diurnal primates combine signals from short-wavelength sensitive (S) cone photoreceptors with signals from medium/long wavelength sensitive (ML) photoreceptors. Three questions about this combination remain unresolved. Firstly, is the combination of S and ML signals in these cells linear or non-linear? Secondly, how does the timing of S and ML inputs to these cells influence their responses? Thirdly, is there spatial antagonism within S and ML subunits of the receptive field of these cells? We measured contrast sensitivity and spatial frequency tuning for four types of drifting sine gratings: S cone isolating, ML cone isolating, achromatic (S + ML), and counterphase chromatic (S - ML), in extracellular recordings from LGN of marmoset monkeys. We found that responses to stimuli which modulate both S and ML cones are well predicted by a linear sum of S and ML signals, followed by a saturating contrast-response relation. Differences in sensitivity and timing (i.e. vector combination) between S and ML inputs are needed to explain the litude and phase of responses to achromatic (S + ML) and counterphase chromatic (S - ML) stimuli. Best-fit spatial receptive fields for S and/or ML subunits in most cells (>80%) required antagonistic surrounds, usually in the S subunit. The surrounds were however generally weak and had little influence on spatial tuning. The sensitivity and size of S and ML subunits were correlated on a cell-by-cell basis, adding to evidence that blue-on and blue-off receptive fields are specialised to signal chromatic but not spatial contrast.
Related Organisations
University College London
Location: United Kingdom of Great Britain and Northern Ireland
Related Funding Activities
Discovery Projects - Grant ID: DP0988227
Start Date: 05-2009
End Date: 09-2013
Amount: $300,000.00
Funder: Australian Research Council
View Funded ActivityDiscovery Projects - Grant ID: DP160104316
Start Date: 05-2016
End Date: 06-2022
Amount: $362,900.00
Funder: Australian Research Council
View Funded ActivityDiscovery Projects - Grant ID: DP160101300
Start Date: 2016
End Date: 12-2019
Amount: $535,117.00
Funder: Australian Research Council
View Funded ActivityARC Centres Of Excellence - Grant ID: CE0561903
Start Date: 2006
End Date: 12-2013
Amount: $16,250,000.00
Funder: Australian Research Council
View Funded ActivityLinkage Infrastructure, Equipment And Facilities - Grant ID: LE0989703
Start Date: 07-2010
End Date: 05-2011
Amount: $500,000.00
Funder: Australian Research Council
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