%0 Journal Article
%~ PubMed
%A Merlin, Sam
%A Horng, Sam
%A Marotte, Lauren R
%A Sur, Mriganka
%A Sawatari, Atomu
%A Leamey, Catherine A
%T Deletion of Ten-m3 Induces the Formation of Eye Dominance Domains in Mouse Visual Cortex.
%B Cerebral Cortex
%D 2013
%C United States
%I Oxford University Press
%V 23
%N 4
%P 763-774
%@ 1460-2199
%X The visual system is characterized by precise retinotopic mapping of each eye, together with exquisitely matched binocular projections. In many species, the inputs that represent the eyes are segregated into ocular dominance columns in primary visual cortex (V1), whereas in rodents, this does not occur. Ten-m3, a member of the Ten-m/Odz/Teneurin family, regulates axonal guidance in the retinogeniculate pathway. Significantly, ipsilateral projections are expanded in the dorsal lateral geniculate nucleus and are not aligned with contralateral projections in Ten-m3 knockout (KO) mice. Here, we demonstrate the impact of altered retinogeniculate mapping on the organization and function of V1. Transneuronal tracing and c-fos immunohistochemistry demonstrate that the subcortical expansion of ipsilateral input is conveyed to V1 in Ten-m3 KOs: Ipsilateral inputs are widely distributed across V1 and are interdigitated with contralateral inputs into eye dominance domains. Segregation is confirmed by optical imaging of intrinsic signals. Single-unit recording shows ipsilateral, and contralateral inputs are mismatched at the level of single V1 neurons, and binocular stimulation leads to functional suppression of these cells. These findings indicate that the medial expansion of the binocular zone together with an interocular mismatch is sufficient to induce novel structural features, such as eye dominance domains in rodent visual cortex.
%Z FOR Codes: 110906


%0 Journal Article
%~ PubMed
%A Lee, Hyunchul
%A Leamey, Catherine A
%A Sawatari, Atomu
%T Perineuronal nets play a role in regulating striatal function in the mouse.
%B PLoS One
%D 2012
%C United States
%I Public Library of Science
%V 7
%N 3
%P e32747
%@ 1932-6203
%X The striatum is the primary input nucleus of the basal ganglia, a collection of nuclei that play important roles in motor control and associative learning. We have previously reported that perineuronal nets (PNNs), aggregations of chondroitin-sulfate proteoglycans (CSPGs), form in the matrix compartment of the mouse striatum during the second postnatal week. This period overlaps with important developmental changes, including the attainment of an adult-like gait. Here, we investigate the identity of the cells encapsulated by PNNs, characterize their topographical distribution and determine their function by assessing the impact of enzymatic digestion of PNNs on two striatum-dependent behaviors: ambulation and goal-directed spatial learning. We show PNNs are more numerous caudally, and that a substantial fraction (41%) of these structures surrounds parvalbumin positive (PV+) interneurons, while approximately 51% of PV+ cells are ensheathed by PNNs. The colocalization of these structures is greatest in dorsal, lateral and caudal regions of the striatum. Bilateral digestion of striatal PNNs led to an increase in both the width and variability of hind limb gait. Intriguingly, this also resulted in an improvement in the acquisition rate of the Morris water maze. Together, these data show that PNNs are associated with specific elements of striatal circuits and play a key role in regulating the function of this important structure in the mouse.
%Z FOR Codes: 110903


%0 Journal Article
%~ PubMed
%A Dharmaratne, Nuwan
%A Glendining, Kelly A
%A Young, Timothy R
%A Tran, Heidi
%A Sawatari, Atomu
%A Leamey, Catherine A
%T Ten-m3 Is Required for the Development of Topography in the Ipsilateral Retinocollicular Pathway.
%B PLoS One
%D 2012
%C United States
%I Public Library of Science
%V 7
%N 9
%P e43083
%@ 1932-6203
%X 
%Z FOR Codes: 110906 110903


%0 Book Section
%A Marotte, Lauren R
%A Waite, Phil ME
%A Leamey, Catherine
%T Australian Marsupials as models of brain development
%B The Neurobiology of Australian Marsupials: Brain evolution in other mammalian radiation
%D 2010
%C United Kingdom
%I Cambridge University Press
%V 
%N 
%P 219-224
%@ 9780521519458
%E Ashwell, Ken WS
%X 
%Z FOR Codes: 60805


%0 Book Section
%A Marotte, Lauren R
%A Leamey, Catherine
%A Waite, Phil ME
%T Somatosensory System
%B The Neurobiology of Australian Marsupials: Brain evolution in other mammalian radiation
%D 2010
%C United Kingdom
%I Cambridge University Press
%V 
%N 
%P 167-183
%@ 9780521519458
%E Ashwell, Ken WS
%X 
%Z FOR Codes: 60805


%0 Journal Article
%~ PubMed
%A Simonetti, Teresa
%A Lee, Hyunchul
%A Bourke, Michael
%A Leamey, Catherine A
%A Sawatari, Atomu
%T Enrichment from birth accelerates the functional and cellular development of a motor control area in the mouse.
%B PloS One
%D 2009
%C United States
%I Public Library of Science
%V 4
%N 8
%P e6780
%@ 1932-6203
%X BACKGROUND: There is strong evidence that sensory experience in early life has a profound influence on the development of sensory circuits. Very little is known, however, about the role of experience in the early development of striatal networks which regulate both motor and cognitive function. To address this, we have investigated the influence of early environmental enrichment on motor development. METHODOLOGY/PRINCIPAL FINDINGS: Mice were raised in standard or enriched housing from birth. For animals assessed as adults, half of the mice had their rearing condition reversed at weaning to enable the examination of the effects of pre- versus post-weaning enrichment. We found that exclusively pre-weaning enrichment significantly improved performance on the Morris water maze compared to non-enriched mice. The effects of early enrichment on the emergence of motor programs were assessed by performing behavioural tests at postnatal day 10. Enriched mice traversed a significantly larger region of the test arena in an open-field test and had improved swimming ability compared to non-enriched cohorts. A potential cellular correlate of these changes was investigated using Wisteria-floribunda agglutinin (WFA) staining to mark chondroitin-sulfate proteoglycans (CSPGs). We found that the previously reported transition of CSPG staining from striosome-associated clouds to matrix-associated perineuronal nets (PNNs) is accelerated in enriched mice. CONCLUSIONS/SIGNIFICANCE: This is the first demonstration that the early emergence of exploratory as well as coordinated movement is sensitive to experience. These behavioural changes are correlated with an acceleration of the emergence of striatal PNNs suggesting that they may consolidate the neural circuits underlying these behaviours. Finally, we confirm that pre-weaning experience can lead to life long changes in the learning ability of mice.
%Z FOR Codes: 110903


%0 Journal Article
%~ PubMed
%A Leamey, Catherine A
%A Van Wart, Audra
%A Sur, Mriganka
%T Intrinsic patterning and experience-dependent mechanisms that generate eye-specific projections and binocular circuits in the visual pathway.
%B Current opinion in neurobiology
%D 2009
%C United Kingdom
%I Elsevier Ltd.
%V 19
%N 2
%P 181-7
%@ 1873-6882
%X 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.
%Z FOR Codes: 110906


%0 Journal Article
%~ PubMed
%A Young, Timothy R
%A Leamey, Catherine A
%T Teneurins: Important regulators of neural circuitry.
%B The international journal of biochemistry & cell biology
%D 2009
%C United Kingdom
%I Pergamon
%V 41
%N 5
%P 990-3
%@ 1357-2725
%X 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.
%Z FOR Codes: 110906


%0 Book Section
%A Leamey, Catherine
%A Protti, Dario
%A Dreher, Bogdan
%T Comparative Survey of the Mammalian Visual System with Reference to the Mouse
%B Eye, Retina, and Visual System of the Mouse
%D 2008
%C United States
%I MIT Press
%V 
%N 
%P 35-60
%@ 9780262033817
%E Chalupa, Leo M.
%E Williams, Robert W.
%X 
%Z FOR Codes: 111301


%0 Journal Article
%~ Isi
%A Lyckman, A. W.
%A Horng, S.
%A Leamey, C. A.
%A Tropea, D.
%A Watakabe, A.
%A Van Wart, A.
%A McCurry, C.
%A Yamamori, T.
%A Sur, M.
%T Gene expression patterns in visual cortex during the critical period: Synaptic stabilization and reversal by visual deprivation
%B Proceedings of the National Academy of Sciences of the United States of America
%D 2008
%C United States
%I National Academy of Sciences
%V 105
%N 27
%P 9409-9414
%@ 1091-6490
%X 
%Z FOR Codes: 110906


%0 Journal Article
%~ PubMed
%A Lee, Hyunchul
%A Leamey, Catherine A
%A Sawatari, Atomu
%T Rapid reversal of chondroitin sulfate proteoglycan associated staining in subcompartments of mouse neostriatum during the emergence of behaviour.
%B PLoS ONE
%D 2008
%C United States
%I Public Library of Science
%V 3
%N 8
%P e3020
%@ 1932-6203
%X BACKGROUND: The neostriatum, the mouse homologue of the primate caudate/putamen, is the input nucleus for the basal ganglia, receiving both cortical and dopaminergic input to each of its sub-compartments, the striosomes and matrix. The coordinated activation of corticostriatal pathways is considered vital for motor and cognitive abilities, yet the mechanisms which underlie the generation of these circuits are unknown. The early and specific targeting of striatal subcompartments by both corticostriatal and nigrostriatal terminals suggests activity-independent mechanisms, such as axon guidance cues, may play a role in this process. Candidates include the chondroitin sulfate proteoglycan (CSPG) family of glycoproteins which have roles not only in axon guidance, but also in the maturation and stability of neural circuits where they are expressed in lattice-like perineuronal nets (PNNs). METHODOLOGY/PRINCIPAL FINDINGS: The expression of CSPG-associated structures and PNNs with respect to neostriatal subcompartments has been examined qualitatively and quantitatively using double-labelling for Wisteria floribunda agglutinin (WFA), and the mu-opioid receptor (muOR), a marker for striosomes, at six postnatal ages in mice. We find that at the earliest ages (postnatal day (P)4 and P10), WFA-positive clusters overlap preferentially with the striosome compartment. By P14, these clusters disappear. In contrast, PNNs were first seen at P10 and continued to increase in density and spread throughout the caudate/putamen with maturation. Remarkably, the PNNs overlap almost exclusively with the neostriatal matrix. CONCLUSIONS/SIGNIFICANCE: This is the first description of a reversal in the distribution of CSPG associated structures, as well as the emergence and maintenance of PNNs in specific subcompartments of the neostriatum. These results suggest diverse roles for CSPGs in the formation of functional corticostriatal and nigrostriatal connectivity within the striosome and matrix compartments of the developing caudate/putamen.
%Z FOR Codes: 110903


%0 Journal Article
%~ PubMed
%A Leamey, C A
%A Flett, D L
%A Ho, S M
%A Marotte, L R
%T Development of structural and functional connectivity in the thalamocortical somatosensory pathway in the wallaby.
%B The European journal of neuroscience
%D 2007
%C UK
%I Blackwell Publishing Ltd.
%V 25
%N 10
%P 3058-70
%@ 0953-816X
%X 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.
%Z FOR Codes:


%0 Journal Article
%~ PubMed
%A Leamey, Catherine A
%A Glendining, Kelly A
%A Kreiman, Gabriel
%A Kang, Ning-Dong
%A Wang, Kuan H
%A Fassler, Reinhard
%A Sawatari, Atomu
%A Tonegawa, Susumu
%A Sur, Mriganka
%T Differential Gene Expression between Sensory Neocortical Areas: Potential Roles for Ten_m3 and Bcl6 in Patterning Visual and Somatosensory Pathways.
%B Cerebral cortex (New York, N.Y. : 1991)
%D 2007
%C UK
%I Oxford University Press
%V 18
%N 
%P 53-66
%@ 1047-3211
%X 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.
%Z FOR Codes: 110999


%0 Journal Article
%~ PubMed
%A Leamey, Catherine A
%A Merlin, Sam
%A Lattouf, Paul
%A Sawatari, Atomu
%A Zhou, Xiaohong
%A Demel, Natasha
%A Glendining, Kelly A
%A Oohashi, Toshitaka
%A Sur, Mriganka
%A Fässler, Reinhard
%T Ten_m3 regulates eye-specific patterning in the mammalian visual pathway and is required for binocular vision.
%B PLoS biology
%D 2007
%C United States
%I Lippincott Williams & Wilkins
%V 5
%N 9
%P e241-e241
%@ 1545-7885
%X Binocular vision requires an exquisite matching of projections from each eye to form a cohesive representation of the visual world. Eye-specific inputs are anatomically segregated, but in register in the visual thalamus, and overlap within the binocular region of primary visual cortex. Here, we show that the transmembrane protein Ten_m3 regulates the alignment of ipsilateral and contralateral projections. It is expressed in a gradient in the developing visual pathway, which is consistently highest in regions that represent dorsal visual field. Mice that lack Ten_m3 show profound abnormalities in mapping of ipsilateral, but not contralateral, projections, and exhibit pronounced deficits when performing visually mediated behavioural tasks. It is likely that the functional deficits arise from the interocular mismatch, because they are reversed by acute monocular inactivation. We conclude that Ten_m3 plays a key regulatory role in the development of aligned binocular maps, which are required for normal vision.
%Z FOR Codes: 110906