ORCID Profile
0000-0002-3390-4933
Current Organisation
University of Sydney
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Systems Physiology | Central Nervous System | Peripheral Nervous System | Simulation And Modelling | Sensory Processes, Perception And Performance | Neurobiology | Neurosciences | Zoology |
Nervous system and disorders | Behavioural and cognitive sciences | Hearing, vision, speech and their disorders | Biological sciences | Mathematical sciences
Publisher: Wiley
Date: 26-06-2003
DOI: 10.1002/NEU.10226
Abstract: In the retinogeniculate pathway of the ferret, in addition to the separation of the inputs from the two eyes to form eye-specific layers, there is also an anatomical segregation of the terminal arbors of on-center retinal ganglion cells from the terminal arbors of off-center retinal ganglion cell axons to form on/off sublaminae. Sublamination normally occurs during postnatal weeks 3-4 and requires the activity of retinal afferents, N-methyl-D-aspartate receptors, nitric oxide synthase, and a target of nitric oxide, cyclic guanosine monophosphate. Calcineurin is a calcium/calmodulin dependent serine, threonine protein phosphatase suggested to mediate NMDA-receptor dependent synaptic plasticity in the hippoc us. We have examined whether calcineurin plays a role during on/off sublamination in the dorsal lateral geniculate nucleus (dLGN) of the ferret. Immunohistochemistry showed that calcineurin expression is transiently up-regulated in dLGN cells and neuropil during the period of on/off sublamination. A functional role for calcineurin during sublamination was investigated by blocking the enzyme locally via intracranial infusion of FK506. Treatment with FK506 during postnatal weeks 3-4 disrupted the appearance of sublaminae. These results suggest that calcineurin may play a role during this process of activity-dependent pattern formation in the visual pathway.
Publisher: Society for Neuroscience
Date: 11-2019
DOI: 10.1523/ENEURO.0478-18.2019
Abstract: Environmental enrichment (EE) has been shown to improve neural function via the regulation of cortical plasticity. Its capacity to induce functional and/or anatomical repair of miswired circuits is unknown. Ten-m3 knock-out (KO) mice exhibit a highly stereotyped and profound miswiring of ipsilateral retinogeniculate axons and associated deficits in binocularly-mediated visual behavior. We determined whether, and when, EE can drive the repair of subcortical wiring deficits by analyzing Ten-m3 KO and wild-type (WT) mice that were enriched for six weeks from adulthood, weaning or birth in comparison to standard-housed (SE) controls. Six weeks of EE initiated from birth, but not later, induced a significant reduction in the area occupied by ipsilateral retinogeniculate terminals in KOs. No EE-induced correction of mistargeted axons was observed at postnatal day (P)7, indicating that this intervention impacts pruning rather than initial targeting of axons. This reduction was most prominent in the ventrolateral region of the dorsal lateral geniculate nucleus (dLGN), suggesting a preferential pruning of the most profoundly mistargeted axons. EE can thus partially repair a specific, subcortical axonal wiring deficit, but only during an early, developmentally-restricted time window.
Publisher: Public Library of Science (PLoS)
Date: 04-09-2007
Publisher: Wiley
Date: 12-1994
Abstract: The development of the vibrissae and their innervation and the maturation of the brainstem trigeminal sensory nuclei have been studied in the wallaby, Macropus eugenii, from birth to adulthood. At birth, developing vibrissal follicles consist of solid epidermal pegs surrounded by dermal condensations. The developing follicles and adjacent skin are innervated by trigeminal afferents. Ten days after birth the follicle contains a dermal papilla and the deep vibrissal nerve can be recognised. A hair cone is present at postnatal day (P) 30 and hairs are apparent on the skin surface by P35. By P63 the deep vibrissal nerve can be seen innervating Merkel cells in the outer root sheath in addition, the first signs of the blood sinus can be recognised. Innervation of the inner conical body and lanceolate and lamellated receptors supplying the mesenchymal sheath and waist region are not seen until P119, when the follicle resembles that seen in the adult. At birth, central processes of the trigeminal ganglion cells have entered the trigeminal tract and extend from the rostral pons to the upper cervical cord. Labelling with a carbocyanine dye at P0 shows afferents extending medially from the tract into the trigeminal subnuclei at all levels. At this stage the trigeminal nuclei appear as areas of increased cell density in the lateral brainstem. By P30-40 the four subnuclei can be distinguished on the basis of shape, cytoarchitecture, and succinic dehydrogenase reactivity. Adult morphology is not fully established until P210. In mature animals, nucleus principalis contains closely packed, polymorphic cells, frequently aligned parallel to thick fibre bundles that traverse the nucleus obliquely. Subnuclei oralis and interpolaris contain sparsely distributed, medium to large cells, randomly oriented, as well as prominent rostrocaudally directed fibre bundles. Subnucleus caudalis consists of the marginal layer, substantia gelatinosa, and magnocellular layers as described in other species. Patches of increased succinic dehydrogenase or cytochrome oxidase reactivity, presumably corresponding to the vibrissae, are present in subnuclei principalis, interpolaris, and caudalis in developing and adult animals, although the pattern is less clear than in rats. The brainstem patches are first seen at P40, approximately 6 weeks before the corresponding vibrissal-related pattern develops in the cortex. This suggests that the onset of patch formation may be regulated independently at different levels of the pathway.
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1016/J.SEMCDB.2014.08.007
Abstract: A functionally critical feature of the nervous system is the precision of its connectivity. An emerging molecular mediator of this process is the teneurin/ten-m/odz family of transmembrane proteins. A number of recent studies have provided compelling evidence that teneurins have homophilic adhesive properties which, together with their corresponding expression patterns in interconnected groups of neurons, enables them to promote appropriate patterns of connectivity. Particularly important roles have been demonstrated in the visual, olfactory and motor systems. This review attempts to relate new insights into the complex biology of these molecules to their roles in the establishment of functional neural circuits.
Publisher: Wiley
Date: 06-06-2013
DOI: 10.1016/J.IJDEVNEU.2013.05.011
Abstract: Retinal projections to the superior colliculus are organised into retinotopic maps. Binocular vision requires that inputs from the two eyes map in register with each other. Studies in mice lacking Ten-m3, a homophilic transmembrane protein, indicate that it plays a key role in this process by influencing ipsilateral projections. The postnatal, ex utero development of the wallaby allows the targeted manipulation of molecules of interest during development. The distribution of mRNA for Ten-m3 in the retina and superior colliculus of the wallaby, and the effects of its spatiotemporally restricted retinal overexpression was investigated, in particular on the mapping of ipsilateral projections. Quantitative polymerase chain reaction found that Ten-m3 mRNA is expressed at relatively higher levels in the retina and colliculus early in development. Further, it is higher in ventral than dorsal retina, and increased in the retinotopically corresponding medial compared to lateral superior colliculus. In situ hybridisation demonstrated an increasing dorsoventral gradient in retinal ganglion cells was matched to an increasing lateromedial gradient in the superior colliculus. Overexpression of Ten-m3 by in vivo retinal electroporation produced an increase in ipsilateral projections to the binocular rostromedial colliculus, fitting with the proposal that Ten-m3 mediates mapping by attractant homophilic interactions. Retrograde labelling of the projection from this region suggested that overexpression produces a shift in the axons of existing ipsilaterally projecting ganglion cells rather than a rerouting of the axons of contralaterally projecting cells. Retinal manipulation of Ten-m3 levels produces changes in ipsilateral mapping, supporting a role for it in binocular mapping.
Publisher: Springer Science and Business Media LLC
Date: 12-2017
Publisher: Elsevier BV
Date: 06-1998
DOI: 10.1016/S0166-2236(97)01217-4
Abstract: In mature rodents, whisker-related patterns are known to be present in three levels of the brain: the brainstem trigeminal nuclei, the ventrobasal thalamus and the somatosensory cortex. These patterns have been demonstrated using neuroanatomical tracing techniques, histological and histochemical staining methods and electrophysiological recordings. The development and topography of these patterns are dependent on an intact periphery. But what governs when patterns form at the three levels? Possibilities include a controlling signal from the periphery or local mechanisms at each site, such as the arrival of afferent inputs or the maturation of target tissue. In this review, we report on the maturation of the whisker pathway in a marsupial, the wallaby, where the slow tempo of development is a feature. At each level, afferent fibres grow into the region of termination many weeks before the whisker-related pattern emerges. The results suggest that the maturity of the target tissue as well as signals from the periphery combine to trigger pattern formation at each level of the pathway.
Publisher: Elsevier BV
Date: 05-2009
DOI: 10.1016/J.BIOCEL.2008.06.014
Abstract: Teneurin (Ten-m/Odz) molecules represent a highly conserved family of four type II transmembrane proteins in vertebrates (Ten-m1-4), which exist as homodimers and undergo homophilic interactions. Each is expressed in distinct, and often interconnected, areas of the developing nervous system. Different Ten-ms have complementary expression patterns. In vitro and in vivo studies support roles for teneurins in promoting neurite outgrowth and cell adhesion. Furthermore, the intracellular domains of at least two teneurins can undergo proteolytic cleavage and translocate to the nucleus where they regulate transcriptional activity. Recent in vivo studies show that teneurins play important roles in regulating connectivity in the nervous system. Knockdown in C. elegans resulted in abnormal axon guidance and cell migration, while targeted deletion of Ten-m3 in mice revealed it is required for the guidance of retinal axons and generation of visual topography. It is likely that all teneurins play important roles during neural development.
Publisher: Cambridge University Press (CUP)
Date: 03-2001
DOI: 10.1017/S0952523801182027
Abstract: Here we examine the patterns of connections between the zona incerta (ZI) of the thalamus and the major visual centers of the rat brain, namely the retina, dorsal lateral geniculate nucleus (LGd), superficial layers of the superior colliculus (SCs), and occipital cortex (Ocl). Injections of the tracers biotinylated dextran or cholera toxin subunit b were made into each of these centers, as well as ZI itself, by using stereotaxic coordinates. Rat brains were then aldehyde-fixed and processed using standard methods. We show that the retina, LGd, SCs, and Ocl all have connections with ZI moreover, that each of these connections make a very distinct territory or subsector within the most lateral ZI regions. This subsector of connectivity with the visual centers does not respect the well-defined cytoarchitectonic sectors of ZI, being made up of small zones in the dorsal, ventral, and caudal sectors. Often, a distinctive "horse-shoe" pattern is evident, particularly after retinal and Ocl injections. Tracer injections into topographically distinct regions of the LGd. SCs, or Ocl results in no shift in the spatial location of labelling within ZI after each injection, labelling is always seen within the lateral edge of the nucleus. Labelled terminals and cells are seen after LGd and SCs injections, while only labelled terminals are seen after retinal and Ocl injections. Although the precise function of this novel visual subsector is not known, these early findings suggest that ZI may be in a position to integrate visual information together with the other somatosensory, motor, and visceral information that it receives.
Publisher: Springer Science and Business Media LLC
Date: 11-11-2022
DOI: 10.1038/S41598-022-23572-4
Abstract: The common final pathway to blindness in many forms of retinal degeneration is the death of the light-sensitive primary retinal neurons. However, the normally light-insensitive second- and third-order neurons persist optogenetic gene therapy aims to restore sight by rendering such neurons light-sensitive. Here, we investigate whether bReaChES, a newly described high sensitivity Type I opsin with peak sensitivity to long-wavelength visible light, can restore vision in a murine model of severe early-onset retinal degeneration. Intravitreal injection of an adeno-associated viral vector carrying the sequence for bReaChES downstream of the calcium calmodulin kinase IIα promoter resulted in sustained retinal expression of bReaChES. Retinal ganglion cells (RGCs) expressing bReaChES generated action potentials at light levels consistent with bright indoor lighting (from 13.6 log photons cm −2 s −1 ). They could also detect flicker at up to 50 Hz, which approaches the upper temporal limit of human photopic vision. Topological response maps of bReaChES-expressing RGCs suggest that optogenetically activated RGCs may demonstrate similar topographical responses to RGCs stimulated by photoreceptor activation. Furthermore, treated dystrophic mice displayed restored cortical neuronal activity in response to light and rescued behavioral responses to a looming stimulus that simulated an aerial predator. Finally, human surgical retinal explants exposed to the bReaChES treatment vector demonstrated transduction. Together, these findings suggest that intravitreal gene therapy to deliver bReaChES to the retina may restore vision in human retinal degeneration in vivo at ecologically relevant light levels with spectral and temporal response characteristics approaching those of normal human photopic vision.
Publisher: Frontiers Media SA
Date: 05-06-2019
Publisher: Frontiers Media SA
Date: 25-02-2020
Publisher: Frontiers Media SA
Date: 24-10-2019
Publisher: Elsevier BV
Date: 04-2014
DOI: 10.1016/J.NEULET.2014.02.048
Abstract: The dorsal lateral geniculate nucleus (dLGN) contains a retinotopic map where input from the two eyes map in register to provide a substrate for binocular vision. Ten-m3, a transmembrane protein, mediates homophilic interactions and has been implicated in the patterning of ipsilateral visual projections. Ease of access to early developmental stages in a marsupial wallaby has been used to manipulate levels of Ten-m3 during the development of retinogeniculate projections. In situ hybridisation showed a high dorsomedial to low ventrolateral gradient of Ten-m3 in the developing dLGN, matching retinotopically with the previously reported high ventral to low dorsal retinal gradient. Overexpression of Ten-m3 in ventronasal but not dorsonasal retina resulted in an extension of ipsilateral projections beyond the normal binocular zone. These results demonstrate that Ten-m3 influences ipsilateral projections and support a role for it in binocular mapping.
Publisher: Public Library of Science (PLoS)
Date: 26-08-2009
Publisher: No publisher found
Date: 1996
DOI: 10.1002/(SICI)1096-9861(19960115)364:3<494::AID-CNE8>3.0.CO;2-%23
Publisher: Public Library of Science (PLoS)
Date: 19-09-2012
Publisher: Public Library of Science (PLoS)
Date: 12-03-2012
Publisher: Springer Science and Business Media LLC
Date: 04-2001
DOI: 10.1038/35067562
Publisher: Oxford University Press (OUP)
Date: 11-04-2013
Publisher: Society for Neuroscience
Date: 12-12-2023
DOI: 10.1523/ENEURO.0162-22.2022
Abstract: Environmental enrichment (EE) is beneficial for brain development and function, but our understanding of its capacity to drive circuit repair, the underlying mechanisms, and how this might vary with age remains limited. Ten-m3 knock-out (KO) mice exhibit a dramatic and stereotyped mistargeting of ipsilateral retinal inputs to the thalamus, resulting in visual deficits. We have recently shown a previously unexpected capacity for EE during early postnatal life (from birth for six weeks) to drive the partial elimination of miswired axonal projections, along with a recovery of visually mediated behavior, but the timeline of this repair was unclear. Here, we reveal that with just 3.5 weeks of EE from birth, Ten-m3 KOs exhibit a partial behavioral rescue, accompanied by pruning of the most profoundly miswired retinogeniculate terminals. Analysis suggests that the pruning is underway at this time point, providing an ideal opportunity to probe potential mechanisms. With the shorter EE-period, we found a localized increase in microglial density and activation profile within the identified geniculate region where corrective pruning was observed. No comparable response to EE was found in age-matched wild-type (WT) mice. These findings identify microglia as a potential mechanistic link through which EE drives the elimination of miswired neural circuits during early postnatal development. Activity driven, atypical recruitment of microglia to prune aberrant connectivity and restore function may have important therapeutic implications for neurodevelopmental disorders such as autistic spectrum disorder.
Publisher: Wiley
Date: 04-2023
DOI: 10.1002/DNEU.22912
Abstract: The patterning of binocular vision requires distinct molecular pathways for inputs arising from each side of the nervous system. Recent studies have demonstrated important roles for members of the Ten‐m/Odz/teneurin family in the development of ipsilateral retinal projections. Here, we further highlight the significance of this gene family in visual development by identifying a role for Ten‐m4 during the formation of the ipsilateral projection in the mouse. Ten‐m4 was found to be expressed in the retina, dorsal lateral geniculate nucleus (dLGN), superior colliculus (SC), and primary visual cortex (V1) during development. Anterograde and retrograde tracing experiments in Ten‐m4 knockout (KO) mice revealed a specific increase in ipsilateral retinal ganglion cells projecting to dLGN and SC. This increase was most prominent in regions corresponding to temporal retina. Consistent with this, EphB1 expression in the retina around the time of decussation was enhanced in this temporal region for KO mice, suggesting that the increased size of the ipsilateral population arises due to an increased number of retinal ganglion cells remaining ipsilaterally at the optic chiasm due to EphB1‐mediated repulsion. The ectopic ipsilaterally targeted retinal ganglion cell projection observed in Ten‐m4 KOs was associated with changes in response to ethologically relevant visual stimuli. Together, these data demonstrate a requirement for Ten‐m4 in the establishment of ipsilateral projections from the retina, which likely acts in combination with other Ten‐m members (Ten‐m2 and Ten‐m3) to promote the formation of functional binocular circuits.
Publisher: Wiley
Date: 05-2007
DOI: 10.1111/J.1460-9568.2007.05556.X
Abstract: Neuronal activity is implicated as a driving force in the development of sensory systems. In order for it to play a developmental role, however, the pathways involved must be capable of transmitting this activity. The relationship between afferent arrival, synapse formation and the onset of chemical neurotransmission has been examined using the advantageous model of a marsupial mammal, the wallaby (Macropus eugenii), to determine at what stage activity has the capacity to influence cortical development. It is known that thalamocortical afferents arrive in the somatosensory cortex on postnatal day (P)15 and that their growth cones reach to the base of the compact cell zone of the cortical plate. However, electronmicroscopy showed that thalamocortical synapses were absent at this stage. Glutamatergic responses were recorded in the cortex following stimulation of the thalamus in slices at this time but only in magnesium-free conditions. The responses were mediated entirely by N-methyl-d-aspartate (NMDA) receptors. From P28, responses could be recorded in normal magnesium and comprised a dominant NMDA-mediated component and a non-NMDA mediated component. At this time thalamocortical synapses were first identified and they were in the cortical plate. By P63 the non-NMDA-mediated component had increased relative to the NMDA-mediated component, and by P70 layer IV began to emerge and contained thalamocortical synapses. By P76 a fast non-NMDA-mediated peak dominated the response. This coincides with the appearance of cortical whisker-related patches and the onset in vivo of responses to peripheral stimulation of the whiskers.
Publisher: Elsevier BV
Date: 02-1998
DOI: 10.1016/S0165-3806(97)00170-3
Abstract: In this study, a novel in vitro slice preparation has been used to study the anatomical and physiological development of the trigeminothalamic pathway in the prenatal and neonatal rat. Anterograde tracing studies showed that the most rostral trigeminal fibres had reached the cephalic flexure by embryonic day (E)15, and entered the diencephalon by E16. By E17 the first few fibres had reached the ventroposteromedial thalamic nucleus (VPM) where they terminated in growth cones. The projection was more substantial and fibres had begun branching by E18, and arbors were more elaborate by E19. The fibres densely filled the nucleus by the day of birth (PO). The physiological studies showed that postsynaptic responses to stimulation of the trigeminal nerve or principal sensory nucleus (Pr5) could first be recorded at E17. Reliable responses to stimulation of either the nerve or Pr5 were recorded from E18 on. Stimulation of Pr5 enabled both axonal and synaptic signals to recorded in VPM. A GABAergic influence was acting to decrease the overall level of excitability in the thalamus from E18. In prenatal animals, the excitatory response was primarily mediated by NMDA receptors, and by P1 a non-NMDA mediated component was beginning to appear. These results demonstrate that the capacity for axonal conduction in the trigeminothalamic fibres and synaptic transmission in the thalamus are present from the time that anatomical connections are first established.
Publisher: Proceedings of the National Academy of Sciences
Date: 08-07-2008
Abstract: The mapping of eye-specific, geniculocortical inputs to primary visual cortex (V1) is highly sensitive to the balance of correlated activity between the two eyes during a restricted postnatal critical period for ocular dominance plasticity. This critical period is likely to have lified expression of genes and proteins that mediate synaptic plasticity. DNA microarray analysis of transcription in mouse V1 before, during, and after the critical period identified 31 genes that were up-regulated and 22 that were down-regulated during the critical period. The highest-ranked up-regulated gene, cardiac troponin C, codes for a neuronal calcium-binding protein that regulates actin binding and whose expression is activity-dependent and relatively selective for layer-4 star pyramidal neurons. The highest-ranked down-regulated gene, synCAM , also has actin-based function. Actin-binding function, G protein signaling, transcription, and myelination are prominently represented in the critical period transcriptome. Monocular deprivation during the critical period reverses the expression of nearly all critical period genes. The profile of regulated genes suggests that synaptic stability is a principle driver of critical period gene expression and that alteration in visual activity drives homeostatic restoration of stability.
Publisher: Wiley
Date: 15-01-1996
DOI: 10.1002/(SICI)1096-9861(19960115)364:3<494::AID-CNE8>3.0.CO;2-#
Abstract: Huntington's disease (HD) has become a target of the first clinical trials for gene therapy among movement disorders with a genetic origin. More than 100 clinical trials regarding HD have been tried, but all failed, although there were some improvements limited to symptomatic support. Compared to other neurogenetic disorders, HD is known to have a single genetic target. Thus, this is an advantage and its cure is more feasible than any other movement disorder with heterogeneous genetic causes. In this review paper, the authors attempt to cover the characteristics of HD itself while providing an overview of the gene transfer methods currently being researched, and will introduce an experimental trial with a preclinical model of HD followed by an update on the ongoing clinical trials for patients with HD.
Publisher: MyJove Corporation
Date: 29-12-2014
DOI: 10.3791/52225
Publisher: Wiley
Date: 20-10-1997
DOI: 10.1002/(SICI)1096-9861(19971020)387:2<194::AID-CNE3>3.0.CO;2-W
Abstract: The development of trigeminal projections between the thalamus and cortex has been investigated in the marsupial mammal, the wallaby, by using a carbocyanine dye, horseradish peroxidase conjugated to wheat germ agglutinin (WGA-HRP), Neurobiotin, and biocytin as pathway tracers. The appearance of whisker-related patterns in the cortex in relation to their appearance in the brainstem and thalamus was examined, as was the presence or absence of a waiting period for thalamocortical afferents and the identity of the first cortical cells to project to the thalamus. Thalamic afferents first reached the cortex at postnatal day (P) 15 and were distributed up to the deep edge of the compact cell zone in the superficial cortical plate throughout development, in both dye and WGA-HRP labelled material, with no evidence of a waiting period. The initial corticothalamic projection, detected by retrograde transport of WGA-HRP from the thalamus, occurred at P60 from layer 5 cells. This was confirmed by labelling of corticothalamic axons after cortical injections of Neurobiotin and biocytin. Scattered, labelled cells seen before P60 after dye labelling from the thalamus presumably resulted from transcellular labelling via thalamic afferents. Clustering of afferents in layer 4 and cell bodies and their dendrites in layers 5 and 6 first occurred simultaneously at P76. There is a sequential onset of pattern formation, first in brainstem, then in thalamus, and finally in cortex, with a long delay between afferent arrival and pattern formation at each level. Independent regulation at each level, likely depending on target maturation, is suggested.
Publisher: Society for Neuroscience
Date: 24-07-2013
Publisher: MyJove Corporation
Date: 26-12-2014
DOI: 10.3791/52220
Publisher: Oxford University Press (OUP)
Date: 02-05-2007
Abstract: Adult neocortical areas are characterized by marked differences in cytoarchitecture and connectivity that underlie their functional roles. The molecular determinants of these differences are largely unknown. We performed a microarray analysis to identify molecules that define the somatosensory and visual areas during the time when afferent and efferent projections are forming. We identified 122 molecules that are differentially expressed between the regions and confirmed by quantitative polymerase chain reaction 95% of the 20 genes tested. Two genes were chosen for further investigation: Bcl6 and Ten_m3. Bcl6 was highly expressed in the superficial cortical plate corresponding to developing layer IV of somatosensory cortex at postnatal day (P) 0. This had diminished by P3, but strong expression was found in layer V pyramidal cells by P7 and was maintained until adulthood. Retrograde tracing showed that Bcl6 is expressed in corticospinal neurons. Ten_m3 was expressed in a graded pattern within layer V of caudal cortex that corresponds well with visual cortex. Retrograde tracing and immunostaining showed that Ten_m3 is highly expressed along axonal tracts of projection neurons of the developing visual pathway. Overexpression demonstrated that Ten_m3 promotes homophilic adhesion and neurite outgrowth in vivo. This suggests an important role for Ten_m3 in the development of the visual pathway.
Publisher: Public Library of Science (PLoS)
Date: 20-08-2008
Publisher: Elsevier BV
Date: 04-2009
DOI: 10.1016/J.CONB.2009.05.006
Abstract: A defining feature of the mammalian nervous system is its complex yet precise circuitry. The mechanisms which underlie the generation of neural connectivity are the topic of intense study in developmental neuroscience. The mammalian visual pathway demonstrates precise retinotopic organization in subcortical and cortical pathways, together with the alignment and matching of eye-specific projections, and sophisticated cortical circuitry that enables the extraction of features underlying vision. New approaches employing molecular-genetic analyses, transgenic mice, novel recombinant probes, and high-resolution imaging are contributing to rapid progress and a new synthesis in the field. These approaches are revealing the ways in which intrinsic patterning mechanisms act in concert with experience-dependent mechanisms to shape visual projections and circuits.
Publisher: Wiley
Date: 14-09-1998
DOI: 10.1002/(SICI)1096-9861(19980914)399:1<47::AID-CNE4>3.0.CO;2-A
Abstract: A light and electron microscopic study has been made of the time of formation of whisker-related patterns in trigeminothalamic afferents and the onset of synapse formation between afferents and cells in the ventroposteromedial nucleus (VPM) of the marsupial mammal, the wallaby, by labelling afferents with a carbocyanine dye. A parallel in vitro study was made of the functional development of the trigeminothalamic pathway to the VPM. Evoked synaptic responses could be recorded in the VPM from the time that afferents first reached the VPM at postnatal day 15 (P15). At all stages, the excitatory response comprised both N-methyl-D-aspartate- and non-N-methyl-D-aspartate-mediated components. At P40, the response decreased markedly in duration, coinciding with the onset of synaptogenesis. This implies that transmission is occurring prior to synapse formation, probably through transmitter release from growth cones. At P50, synaptic responses became dominated by a fast, non-N-methyl-D-aspartate potential, and this coincided with the first appearance of whisker-related patterns in the VPM. A gamma-aminobutyric acid (subtype A)-mediated, inhibitory component was also present from the time of afferent arrival. These findings support the idea that functional interactions between afferents and their targets may play a role in pattern formation in the somatosensory thalamus.
Publisher: Frontiers Media SA
Date: 15-03-2018
Publisher: Wiley
Date: 18-11-2015
DOI: 10.1111/EJN.12767
Abstract: The striatum is the key input nucleus of the basal ganglia, and is implicated in motor control and learning. Despite the importance of striatal circuits, the mechanisms associated with their development are not well established. Previously, Ten-m3, a member of the Ten-m/teneurin/odz family of transmembrane glycoproteins, was found to be important in the mapping of binocular visual pathways. Here, we investigated a potential role for Ten-m3 in striatal circuit formation. In situ hybridisation revealed a patchy distribution of Ten-m3 mRNA expression superimposed on a high-dorsal to low-ventral gradient in a subregion of the striatal matrix. A survey of afferent/efferent structures associated with the matrix identified the parafascicular thalamic nucleus (PF) as a potential locus of action. Ten-m3 was also found to be expressed in a high-dorsal to low-ventral gradient in the PF, corresponding topographically to its expression in the striatum. Further, a subset of thalamic terminal clusters overlapped with Ten-m3-positive domains within the striatal matrix. Studies in wild-type (WT) and Ten-m3 knockout (KO) mice revealed no differences in overall striatal or PF structure. Thalamostriatal terminals in KOs, however, while still confined to the matrix subregion, lost their clustered appearance. Topography was also altered, with terminals from the lateral PF projecting ectopically to ventral and medial striatum, rather than remaining confined dorsolaterally as in WTs. Behaviorally, Ten-m3 KOs displayed delayed motor skill acquisition. This study demonstrates that Ten-m3 plays a key role in directing the formation of thalamostriatal circuitry, the first molecular candidate reported to regulate connectivity within this pathway.
Start Date: 07-2010
End Date: 05-2011
Amount: $500,000.00
Funder: Australian Research Council
View Funded ActivityStart Date: 2004
End Date: 12-2004
Amount: $10,000.00
Funder: Australian Research Council
View Funded Activity