ORCID Profile
0000-0003-3676-657X
Current Organisations
Florey Institute of Neuroscience and Mental Health
,
University of Melbourne
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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)
Cellular Nervous System | Neurosciences | Central Nervous System | Cellular nervous system | Sensory Systems | Central nervous system | Neurosciences
ANZSRC Socio-Economic Objective (SEO)
Expanding Knowledge in the Biological Sciences | Expanding Knowledge in the Medical and Health Sciences |
Related Links
Publications
Dendrites
Publisher: Oxford University Press
Date: 03-2016
LINE-1 retrotransposon activation intrinsic to interneuron development
Publisher: Cold Spring Harbor Laboratory
Date: 20-03-2022
DOI: 10.1101/2022.03.20.485017
Abstract: Transposable elements (TEs) are a reservoir of new transcription factor binding sites for protein-coding genes 1–3 . Developmental programs that activate TE-derived regulatory elements could, in principle, manifest in lineage-specific TE mobility. While somatic LINE-1 (L1) retrotransposon insertions have been detected in human neurons 4–6 , the impact of L1 insertions on neurodevelopmental gene regulation, and whether L1 mobility is restricted to certain neuronal lineages, is unknown. Here, we reveal programmed L1 activation by SOX6, a transcription factor critical for parvalbumin (PV + ) interneuron development 7–9 . PV + neurons harbor unmethylated and euchromatic L1 promoters, express L1 mRNA, and permit L1 transgene mobilization in vivo . Elevated L1 expression in adult dentate gyrus PV + neurons is however attenuated by environmental enrichment. Nanopore sequencing of PV + neurons identifies unmethylated L1 loci providing alternative promoters to core PV + neuron genes, such as CAPS2. These data depict SOX6-mediated L1 activation as an ingrained component of the mammalian PV + neuron developmental program.
Design and performance of an ultra-flexible two-photon microscope for in vivo research
Publisher: The Optical Society
Date: 02-10-2015
DOI: 10.1364/BOE.6.004228
Dendritic integration in pyramidal neurons during network activity and disease
Publisher: Elsevier BV
Date: 04-2014
DOI: 10.1016/J.BRAINRESBULL.2013.09.010
Abstract: Neurons have intricate dendritic morphologies which come in an array of shapes and sizes. Not only do they give neurons their unique appearance, but dendrites also endow neurons with the ability to receive and transform synaptic inputs. We now have a wealth of information about the functioning of dendrites which suggests that the integration of synaptic inputs is highly dependent on both dendritic properties and neuronal input patterns. It has been shown that dendrites can perform non-linear processing, actively transforming synaptic input into Na(+) spikes, Ca(2+) plateau spikes and NMDA spikes. These membrane non-linearities can have a large impact on the neuronal output and have been shown to be regulated by numerous factors including synaptic inhibition. Many neuropathological diseases involve changes in how dendrites receive and package synaptic input by altering dendritic spine characteristics, ion channel expression and the inhibitory control of dendrites. This review focuses on the role of dendrites in integrating and transforming input and what goes wrong in the case of neuropathological diseases.
Imaging membrane potential in dendrites and axons of single neurons
Publisher: Springer Science and Business Media LLC
Date: 26-09-2006
DOI: 10.1007/S00424-006-0149-3
Abstract: This review focuses on the use of imaging techniques to record electrical signaling in the fine processes of neurons such as dendrites and axons. Voltage imaging began with the use and development of externally applied voltage-sensitive dyes. With the introduction of internally applied dyes and advances in detection technology, it is now possible to record supra-threshold action potential responses, as well as sub-threshold synaptic potentials, in fine neuronal processes including dendritic spines. The development of genetically coded sensors, as well as variants of laser scanning microscopy such as second harmonic generation, offers promise for further advances in this field. Through the use and further development of these methods, optical imaging of membrane potential will continue to be a valuable tool for investigators wishing to explore the electrical events underlying single neuronal computation.
Two-photon imaging of dendritic calcium dynamics in vivo
Publisher: Springer New York
Date: 2019
Membrane potential changes in dendritic spines during action potentials and synaptic input
Publisher: Society for Neuroscience
Date: 27-05-2009
DOI: 10.1523/JNEUROSCI.5847-08.2009
Abstract: Excitatory input onto many neurons in the brain occurs onto specialized projections called dendritic spines. Despite their potential importance in neuronal function, direct experimental evidence on electrical signaling in dendritic spines is lacking as their small size makes them inaccessible to standard electrophysiological techniques. Here, we investigate electrical signaling in dendritic spines using voltage-sensitive dye imaging in cortical pyramidal neurons during backpropagating action potentials and synaptic input. Backpropagating action potentials were found to fully invade dendritic spines without voltage loss. The voltage change in dendritic spines during synaptic input ranged from a few millivolts up to ∼20 mV. During hyperpolarization of the membrane potential, the litude of the synaptic voltage in spines was increased, consistent with the expected change resulting from the increased driving force. This observation suggests that voltage-activated channels do not significantly boost the voltage response in dendritic spines during synaptic input. Finally, we used simulations of our experimental observations in morphologically realistic models to estimate spine neck resistance. These simulations indicated that spine neck resistance ranges up to ∼500 MΩ. Spine neck resistances of this magnitude reduce somatic EPSPs by %, indicating that the spine neck is unlikely to act as a physical device to significantly modify synaptic strength.
Probing Cortical Activity During Head-Fixed Behavior
Publisher: Frontiers Media SA
Date: 28-02-2020
Cocaine regulates sensory filtering in cortical pyramidal neurons
Publisher: Elsevier BV
Date: 02-2023
Intracellular calcium release: A conductor of compartmentalized dendritic plasticity
Publisher: Elsevier BV
Date: 05-2022
DOI: 10.1016/J.CELL.2022.04.027
Abstract: Dendrites endow neurons with multiple compartments within their elaborate morphologies. In a recent study published in the journal Science, O'Hare et al. (2022) used elegant techniques to show that augmenting the intracellular calcium released by the endoplasmic reticulum caused behaviorally relevant plasticity to occur in spatially distinct dendritic compartments.
A thalamocortical pathway controlling impulsive behavior
Publisher: Elsevier BV
Date: 09-2023
Higher synaptic threshold for NMDA spike generation in human neurons
Publisher: Cold Spring Harbor Laboratory
Date: 23-10-2021
DOI: 10.1101/2021.10.22.465509
Abstract: Neurons receive synaptic input primarily onto their dendrites. While we know much about the electrical properties of dendrites in rodents, we have only just started to describe their properties in the human brain. Here we investigate the capacity of human neurons to generate NMDA spikes. We find that dendritic iontophoresis of glutamate, as well as local dendritic synaptic stimulation, can evoke NMDA spikes in dendrites of human layer 2/3 pyramidal neurons. Surprisingly, however, the capacity to evoke NMDA spikes in human neurons was significantly reduced compared to that in rodent neurons. Simulations in morphologically realistic models indicated that human neurons have a higher synaptic threshold for NMDA spike generation. Using a simplified model, we show that this is primarily due to the larger diameter of human dendrites. In summary, we find reduced NMDA spike generation in human compared to rodent neurons due to the larger diameter of human dendrites.
Dendritic Compartmentalization of Learning-Related Plasticity
Publisher: Society for Neuroscience
Date: 05-2022
DOI: 10.1523/ENEURO.0060-22.2022
Abstract: The dendrites of cortical pyramidal neurons receive synaptic inputs from different pathways that are organized according to their laminar target. This architectural scheme provides cortical neurons with a spatial mechanism to separate information, which may support neural flexibility required during learning. Here, we investigated layer-specific plasticity of sensory encoding following learning by recording from two different dendritic compartments, tuft and basal dendrites, of layer 2/3 (L2/3) pyramidal neurons in the auditory cortex of mice. Following auditory fear conditioning, auditory-evoked Ca 2+ responses were enhanced in tuft, but not basal, dendrites leading to increased somatic action potential output. This is in direct contrast to the long held (and debated) hypothesis that, despite extensive dendritic arbors, neurons function as a simple one-compartment model. Two computational models of varying complexity based on the experimental data illustrated that this learning-related increase of auditory responses in tuft dendrites can account for the changes in somatic output. Taken together, we illustrate that neurons do not function as a single compartment, and dendritic compartmentalization of learning-related plasticity may act to increase the computational power of pyramidal neurons.
Dendrites: Recording from Fine Neuronal Structures Using Patch-Clamp and Imaging Techniques
Publisher: Springer New York
Date: 2016
A Reward-Based Behavioral Platform to Measure Neural Activity during Head-Fixed Behavior
Publisher: Frontiers Media SA
Date: 31-05-2017
High synaptic threshold for dendritic NMDA spike generation in human layer 2/3 pyramidal neurons
Publisher: Elsevier BV
Date: 12-2022
Effect of the Anesthetic Tricaine (MS-222) on Nerve Activity in the Anterior Lateral Line of the Oyster Toadfish,Opsanus tau
Publisher: American Physiological Society
Date: 08-2004
Abstract: Inductive neural telemetry was used to record from microwire electrodes chronically implanted into the anterior lateral line nerve of the toadfish, Opsanus tau. Spontaneous neural activity and the response of lateral line fibers to water current were continually monitored from 17 primary afferent fibers before, during, and after the administration of the anesthetic tricaine (MS-222). Significant decrease in spontaneous and evoked activity and increase in interspike interval was noted when anesthetic concentrations were ≥0.010%. Neural activity returned to control levels within ∼90 min of anesthetic withdrawal. Decreasing the pH of the solution without the anesthetic caused transient heightened sensitivity, indicating that tricaine and not the concurrent drop in pH was responsible for the decrease in sensitivity during anesthesia. During a secondary challenge with the anesthetic 24 h after the first, fibers initially showed faster recovery however overall recovery kinetics were similar. Although high tricaine concentration was correlated with decreased neural sensitivity, the concentrations normally used to maintain anesthesia in the toadfish did not have significant effect on the evoked firing rate. Thus given sufficient time to recover from the induction of surgical anesthesia, it may be possible to maintain the animal under light anesthesia while minimizing the physiological effects of tricaine.
Initiation of simple and complex spikes in cerebellar Purkinje cells
Publisher: Wiley
Date: 15-05-2010
Early Exposure to Alcohol Leads to Permanent Impairment of Dendritic Excitability in Neocortical Pyramidal Neurons
Publisher: Society for Neuroscience
Date: 25-01-2012
DOI: 10.1523/JNEUROSCI.5520-11.2012
Abstract: Exposure to alcohol in utero is a well known cause of mental retardation in humans. Using experimental models of fetal alcohol spectrum disorder, it has been demonstrated that cortical pyramidal neurons and their projections are profoundly and permanently impaired. Yet, how the functional features of these cells are modified and how such modifications impact cognitive processes is still unknown. To address this, we studied the intrinsic electrophysiological properties of pyramidal neurons in young adult rats (P30–P60) exposed to ethanol inhalation during the first week of postnatal life (P2–P6). Dual whole-cell recordings from the soma and distal apical dendrites were performed and, following the injection of depolarizing current into the dendrites, layer 5 neurons from ethanol-treated (Et) animals displayed a lower number and a shorter duration of dendritic spikes, attributable to a downregulation of calcium electrogenesis. As a consequence, the mean number of action potentials recorded at the soma after dendritic current injection was also lower in Et animals. No significant differences between Et and controls were observed in the firing pattern elicited in layer 5 neurons by steps of depolarizing somatic current, even though the firing rate was significantly lower in Et animals. The firing pattern and the firing rate of layer 2/3 neurons were not affected by alcohol exposure.
Site of action potential initiation in layer 5 pyramidal neurons
Publisher: Society for Neuroscience
Date: 08-02-2006
DOI: 10.1523/JNEUROSCI.4812-05.2006
Abstract: Fundamental to an understanding of how neurons integrate synaptic input is the knowledge of where within a neuron this information is converted into an output signal, the action potential. Although it has been known for some time that action potential initiation occurs within the axon of neurons, the precise location has remained elusive. Here, we provide direct evidence using voltage-sensitive dyes that the site of action potential initiation in cortical layer 5 pyramidal neurons is ∼35 μm from the axon hillock. This was the case during action potential generation under a variety of conditions, after axonal inhibition, and at different stages of development. Once initiated action potentials propagated down the axon in a saltatory manner. Experiments using local application of low-sodium solution and TTX, as well as an investigation of the influence of axonal length on action potential properties, provided evidence that the initial 40 μm of the axon is essential for action potential generation. To morphologically identify the relationship between the site of action potential initiation and axonal myelination, we labeled oligodendrocytes supplying processes to the proximal region of the axon. These experiments indicated that the axon initial segment was ∼40 μm in length, and the first node of Ranvier was ∼90 μm from the axon hillock. Experiments targeting the first node of Ranvier suggested it was not involved in action potential initiation. In conclusion, these results indicate that, in layer 5 pyramidal neurons, action potentials are generated in the distal region of the axon initial segment.
Auditory input enhances somatosensory encoding and tactile goal-directed behavior
Publisher: Springer Science and Business Media LLC
Date: 23-07-2021
DOI: 10.1038/S41467-021-24754-W
Abstract: The capacity of the brain to encode multiple types of sensory input is key to survival. Yet, how neurons integrate information from multiple sensory pathways and to what extent this influences behavior is largely unknown. Using two-photon Ca 2+ imaging, optogenetics and electrophysiology in vivo and in vitro, we report the influence of auditory input on sensory encoding in the somatosensory cortex and show its impact on goal-directed behavior. Monosynaptic input from the auditory cortex enhanced dendritic and somatic encoding of tactile stimulation in layer 2/3 (L2/3), but not layer 5 (L5), pyramidal neurons in forepaw somatosensory cortex (S1). During a tactile-based goal-directed task, auditory input increased dendritic activity and reduced reaction time, which was abolished by photoinhibition of auditory cortex projections to forepaw S1. Taken together, these results indicate that dendrites of L2/3 pyramidal neurons encode multisensory information, leading to enhanced neuronal output and reduced response latency during goal-directed behavior.
Author response: The role of higher-order thalamus during learning and correct performance in goal-directed behavior
Publisher: eLife Sciences Publications, Ltd
Date: 02-03-2022
NMDA spikes enhance action potential generation during sensory input
Publisher: Springer Science and Business Media LLC
Date: 02-02-2014
DOI: 10.1038/NN.3646
Abstract: Recent evidence in vitro suggests that the tuft dendrites of pyramidal neurons are capable of evoking local NMDA receptor-dependent electrogenesis, so-called NMDA spikes. However, it has so far proved difficult to demonstrate their existence in vivo. Moreover, it is not clear whether NMDA spikes are relevant to the output of pyramidal neurons. We found that local NMDA spikes occurred in tuft dendrites of layer 2/3 pyramidal neurons both spontaneously and following sensory input, and had a large influence on the number of output action potentials. Using two-photon activation of an intracellular caged NMDA receptor antagonist (tc-MK801), we found that isolated NMDA spikes typically occurred in multiple branches simultaneously and that sensory stimulation substantially increased their probability. Our results demonstrate that NMDA receptors have a vital role in coupling the tuft region of the layer 2/3 pyramidal neuron to the cell body, enhancing the effectiveness of layer 1 input.
Transcranial magnetic stimulation (TMS) inhibits cortical dendrites
Publisher: eLife Sciences Publications, Ltd
Date: 18-03-2016
DOI: 10.7554/ELIFE.13598
Abstract: One of the leading approaches to non-invasively treat a variety of brain disorders is transcranial magnetic stimulation (TMS). However, despite its clinical prevalence, very little is known about the action of TMS at the cellular level let alone what effect it might have at the subcellular level (e.g. dendrites). Here, we examine the effect of single-pulse TMS on dendritic activity in layer 5 pyramidal neurons of the somatosensory cortex using an optical fiber imaging approach. We find that TMS causes GABAB-mediated inhibition of sensory-evoked dendritic Ca2+ activity. We conclude that TMS directly activates fibers within the upper cortical layers that leads to the activation of dendrite-targeting inhibitory neurons which in turn suppress dendritic Ca2+ activity. This result implies a specificity of TMS at the dendritic level that could in principle be exploited for investigating these structures non-invasively.
High Synaptic Threshold for NMDA Spike Generation in Human Layer 2/3 Pyramidal Neurons
Publisher: Elsevier BV
Date: 2022
DOI: 10.2139/SSRN.4072039
Inhibitory Regulation of Dendritic Activity in vivo
Publisher: Frontiers Media SA
Date: 2012
Neural basis of anticipation and premature impulsive action in the frontal cortex
Publisher: Springer Science and Business Media LLC
Date: 14-11-2022
DOI: 10.1038/S41593-022-01198-Z
Abstract: Planning motor actions can improve behavioral performance however, it can also lead to premature actions. Although the anterior lateral motor cortex (ALM) is known to be important for correct motor planning, it is currently unknown how it contributes to premature impulsive motor output. This was addressed using whole-cell voltage recordings from layer 2/3 pyramidal neurons within the ALM while mice performed a cued sensory association task. Here, a robust voltage response was evoked during the auditory cue, which was greater during incorrect premature behavior than during correct performance in the task. Optogenetically suppressing ALM during the cued sensory association task led to enhanced behavior, with fewer, and more delayed, premature responses and faster correct responses. Taken together, our findings extend the current known roles of the ALM, illustrating that ALM plays an important role in impulsive behavior by encoding and influencing premature motor output.
Layer-specific regulation of cortical neurons by interhemispheric inhibition
Publisher: Informa UK Limited
Date: 13-05-2013
DOI: 10.4161/CIB.23545
Dendritic Mechanisms forIn VivoNeural Computations and Behavior
Publisher: Society for Neuroscience
Date: 09-11-2022
DOI: 10.1523/JNEUROSCI.1132-22.2022
Abstract: Dendrites receive the vast majority of a single neuron's inputs, and coordinate the transformation of these signals into neuronal output. Ex vivo and theoretical evidence has shown that dendrites possess powerful processing capabilities, yet little is known about how these mechanisms are engaged in the intact brain or how they influence circuit dynamics. New experimental and computational technologies have led to a surge in interest to unravel and harness their computational potential. This review highlights recent and emerging work that combines established and cutting-edge technologies to identify the role of dendrites in brain function. We discuss active dendritic mediation of sensory perception and learning in neocortical and hippoc al pyramidal neurons. Complementing these physiological findings, we present theoretical work that provides new insights into the underlying computations of single neurons and networks by using biologically plausible implementations of dendritic processes. Finally, we present a novel brain–computer interface task, which assays somatodendritic coupling to study the mechanisms of biological credit assignment. Together, these findings present exciting progress in understanding how dendrites are critical for in vivo learning and behavior, and highlight how subcellular processes can contribute to our understanding of both biological and artificial neural computation.
Higher order thalamus encodes correct goal-directed action
Publisher: Cold Spring Harbor Laboratory
Date: 06-07-2020
DOI: 10.1101/2020.07.05.188821
Abstract: The thalamus is the gateway to the cortex. Cortical encoding of sensory information can therefore only be understood by considering the influence of thalamic processing on sensory input. Despite modulating sensory processing, little is known about the role of the thalamus during sensory-based behavior, let alone goal-directed behavior. Here, we use two-photon Ca 2+ imaging, patch-cl electrophysiology and optogenetics to investigate the role of axonal projections from the posteromedial nucleus of the thalamus (POm) to the forepaw area of the primary somatosensory cortex (forepaw S1) during sensory processing and goal-directed behavior. We demonstrate that POm axons are active during tactile stimulus and increase activity specifically during the response and, to a lesser extent, reward epochs of a tactile goal-directed task. Furthermore, POm axons in forepaw S1 preferentially signaled correct behavior, with greatest activity during HIT responses. This activity is important for behavioral performance, as photoinhibition of archaerhodopsin-expressing neurons in the POm decreased overall behavioral success. Direct juxtacelluar recordings in the awake state illustrates POm neurons fire sustained action potentials during tactile stimulus. This tactile-evoked POm firing pattern was used during ChR2 photoactivation of POm axons in forepaw S1, revealing that action potentials in layer 2/3 (L2/3) pyramidal neurons are inhibited during sustained POm input. Taken together, POm axonal projections in forepaw S1 encode correct goal-directed active behavior, leading to GABA A -mediated inhibition of L2/3 pyramidal neurons.
Sensitivity of the anterior lateral line to natural stimuli in the oyster toadfish, Opsanus tau (Linnaeus)
Publisher: The Company of Biologists
Date: 15-09-2005
DOI: 10.1242/JEB.01766
Abstract: Inductive neural telemetry was used to record from microwire electrodes chronically implanted into the anterior lateral line nerve of the oyster toadfish, Opsanus tau (L.). The lateral lines of free-ranging toadfish were stimulated by the swimming movements of a prey fish(Fundulus heteroclitus), and the corresponding neural activity was quantified. Both spontaneously active and silent afferent fibers experienced an increase in neural firing as the prey approached the lateral line. Activity was evoked when the prey fish approached to within 8-12 cm of the neuromast,with increases in nerve firing rates directly correlated with diminishing distance. Thus, adult toadfish (28 cm standard length 33 cm total length)were only able to detect mobile prey that approached within approximately 40%of their body length. Both spontaneously active and silent afferent fibers also experienced a dramatic increase in firing during predatory strikes,indicating that the fibers were not inhibited during rapid body movement. This study investigates, for the first time, the neural response of the anterior lateral line to prey stimuli in free-ranging fish.
The Cellular Basis of GABA B -Mediated Interhemispheric Inhibition
Publisher: American Association for the Advancement of Science (AAAS)
Date: 24-02-2012
Abstract: The two hemispheres of the brain are connected via the corpus callosum however, this pathway and its function are still not fully understood. Palmer et al. (p. 989 ) used a combination of optogenetic, calcium-imaging, and electrophysiological methods to investigate the cellular mechanism of interhemispheric inhibition of the firing frequency of neocortical layer 5 pyramidal neurons in rats in vivo and in vitro. They discovered that this form of inhibition involved interneurons in the top layers of the cortex that suppressed active dendritic currents synergistically recruited by back-propagating action potentials. This mechanism depended upon a γ-aminobutyric acid type B receptor–mediated mechanism acting on specific ion channels in the dendrites of pyramidal neurons.
GABAB-mediated inhibition of dendritic activity in vivo
Publisher: Elsevier BV
Date: 09-2011
Local and Global Dynamics of Dendritic Activity in the Pyramidal Neuron
Publisher: Elsevier BV
Date: 05-2022
DOI: 10.1016/J.NEUROSCIENCE.2021.07.008
Abstract: There has been increasing interest in the measurement and comparison of activity across compartments of the pyramidal neuron. Dendritic activity can occur both locally, on a single dendritic segment, or globally, involving multiple compartments of the single neuron. Little is known about how these dendritic dynamics shape and contribute to information processing and behavior. Although it has been difficult to characterize local and global activity in vivo due to the technical challenge of simultaneously recording from the entire dendritic arbor and soma, the rise of calcium imaging has driven the increased feasibility and interest of these experiments. However, the distinction between local and global activity made by calcium imaging requires careful consideration. In this review we describe local and global activity, discuss the difficulties and caveats of this distinction, and present the evidence of local and global activity in information processing and behavior.
Dendritic integration in vivo
Publisher: Oxford University Press
Date: 03-2016
Neural Recordings From the Lateral Line in Free-Swimming Toadfish, Opsanus tau
Publisher: University of Chicago Press
Date: 10-2003
DOI: 10.2307/1543260
Cortical hyperexcitability drives dying forward ALS symptoms and pathology in mice
Publisher: Cold Spring Harbor Laboratory
Date: 14-08-2021
DOI: 10.1101/2021.08.13.456320
Abstract: Amyotrophic lateral sclerosis (ALS) is a progressive fatal disorder caused by degeneration of motor neurons in the cortex and spinal cord. The origin of ALS in the central nervous system is unclear, however cortical hyperexcitability appears as an early and intrinsic feature of ALS and has been linked to degeneration of spinal motor neurons via a dying-forward mechanism. Here, we implement chemogenetics to validate the dying forward hypothesis of ALS in mice. We show that chronic hyperexcitability of corticomotoneurons induced by excitatory chemogenetics results in motor symptoms and core neuropathological hallmarks of ALS, including corticomotoneuron loss, corticospinal tract degeneration and reactive gliosis. Importantly, corticomotoneuron loss was sufficient to drive degeneration of spinal motor neurons and neuromuscular junctions (NMJs), associated with cytoplasmic TAR DNA binding protein 43 (TDP-43) pathology. These findings establish a cortical origin of ALS mediated by neuronal hyperexcitability, consistent with a dying forward mechanism of neurodegeneration.
The role of higher-order thalamus during learning and correct performance in goal-directed behavior
Publisher: eLife Sciences Publications, Ltd
Date: 08-03-2022
DOI: 10.7554/ELIFE.77177
Abstract: The thalamus is a gateway to the cortex. Cortical encoding of complex behavior can therefore only be understood by considering the thalamic processing of sensory and internally generated information. Here, we use two-photon Ca 2+ imaging and optogenetics to investigate the role of axonal projections from the posteromedial nucleus of the thalamus (POm) to the forepaw area of the mouse primary somatosensory cortex (forepaw S1). By recording the activity of POm axonal projections within forepaw S1 during expert and chance performance in two tactile goal-directed tasks, we demonstrate that POm axons increase activity in the response and, to a lesser extent, reward epochs specifically during correct HIT performance. When performing at chance level during learning of a new behavior, POm axonal activity was decreased to naive rates and did not correlate with task performance. However, once evoked, the Ca 2+ transients were larger than during expert performance, suggesting POm input to S1 differentially encodes chance and expert performance. Furthermore, the POm influences goal-directed behavior, as photoinactivation of archaerhodopsin-expressing neurons in the POm decreased the learning rate and overall success in the behavioral task. Taken together, these findings expand the known roles of the higher-thalamic nuclei, illustrating the POm encodes and influences correct action during learning and performance in a sensory-based goal-directed behavior.
Related Organisations
Charite Universitatsmedizin Berlin Klinik Für Neurologie Mit Experimenteller Neurologie
Location: Germany
Florey Institute Of Neuroscience And Mental Health
Location: Australia
Related Funding Activities
Discovery Projects - Grant ID: DP190103296
Start Date: 06-2019
End Date: 12-2023
Amount: $490,000.00
Funder: Australian Research Council
View Funded ActivityARC Future Fellowships - Grant ID: FT230100476
Start Date: 07-2023
End Date: 06-2027
Amount: $1,124,670.00
Funder: Australian Research Council
View Funded ActivityDiscovery Projects - Grant ID: DP160103047
Start Date: 06-2016
End Date: 12-2019
Amount: $399,400.00
Funder: Australian Research Council
View Funded Activity