Symposium
Cortical circuit development:role of thalamocortical input
シンポジウム
大脳皮質の回路形成:視床からの入力の役割 |
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| 7月28日（日）8:45～9:15 第5会場（朱鷺メッセ 3F 302）
4S05m-1
Development and function of Phox2a+ spinofugal nociceptive projection neurons
Artur Kania（Kania Artur）1,2，Brian R. Roome（Roome Brian R.）1,2，Shima Rastegar-Pouyani（Rastegar-Pouyani Shima）1,2，Susana Sotocinal（Sotocinal Susana）2，Annie Dumouchel（Dumouchel Annie）1，W. Scott Thompson（Thompson W. Scott）1，Jean-Francois Brunet（Brunet Jean-Francois）3，Marie Kmita（Kmita Marie）1，Jeff Mogil（Mogil Jeff）2
1Institut de recherches cliniques de Montreal (IRCM), Montreal, Canada
2McGill University, Montreal, Canada
3Ecole Normale Superieure, Paris, France
The relay of nociceptive signals from spinal neuronal circuits to the brain remains poorly understood. Classical experiments demonstrate that spinal dorsal horn projection neurons relay such signals to the parabrachial nucleus, thalamus, periaqueductal gray and other brain regions. To directly study the specific function of these pathways, we generated a Phox2a:Cre transgenic mouse line expressing Cre recombinase from the Paired-like Homeobox 2a (Phox2a) locus that encodes a developmentally-expressed transcription factor. Phox2a:Cre labels neurons in Lamina I and V of the spinal cord exhibiting classical projection neuron morphology. At least 90% of Phox2a:Cre neurons are spinofugal projection neurons, demonstrated by retrograde tracing from supraspinal locations involved in nociception. Chemogenetic activation and silencing of spinal Phox2a:Cre neurons results in behavioural effects consistent with their role in relaying nociceptive signals from the spinal cord to the brain.
Phox2a is expressed in early postmitotic neurons of the spinal dI5 lineage prompting us to examine its developmental function in the specification of diverse spinofugal pathways. To do this, we (1) began molecular profiling of Phox2a-expressing embryonic neurons, and (2) are analysing the specification of spinofugal projection neurons, their connectivity and adult function in conditional knockouts of Phox2a using the Phox2a:Cre and spinal cord-specific Hoxb8:Cre drivers. Together our experiments provide insights into the dissection of emotive, discriminative, motor and homeostatic components of pain, and into the development of some of the longest axonal connections in the nervous system. | | 7月28日（日）9:15～9:45 第5会場（朱鷺メッセ 3F 302）
4S05m-2
Organization of mouse dLGN: circuits underlying a faithful relay and active filtering of retinal signaling to visual cortex.
William Guido（Guido William）
Anatomical Sciences and Neurobiology, University of Louisville, KY, USA
The dorsal lateral geniculate nucleus (dLGN) is the thalamic relay linking the retina to the visual cortex. Within the past decade the mouse has emerged as a model system to understand many aspects about the development, structural composition, and functional operations of sensory thalamic nuclei. Aided by the advance of molecular tools and the widespread availability of transgenic lines, studies in mouse allow unprecedented access to interrogate specific cell types, circuits, and projections. Studies in mouse provide further support that the dLGN is more than a simple relay of visual information. The visual response properties of dLGN neurons are far more diverse and sophisticated than previously recognized, and much like the dLGN of higher mammals, the mouse dLGN receives most of its input from nonretinal sources that operate to modulate the gain of retinogeniculate signal transmission. The purpose of this talk is to delineate the circuits underlying these operations. | | 7月28日（日）9:45～10:15 第5会場（朱鷺メッセ 3F 302）
4S05m-3
視床軸索は大脳皮質細胞の多様性を生む
Tomomi Shimogori（下郡 智美），Timothy R Young（Young R Timothy）
理化学研究所 脳神経科学研究センター
The mammalian neocortex displays considerable diversification in its cell types, underlying the complexity of neural circuits involved in processing of information within different brain regions. What gives rise to such neuronal diversity seen across and within cortical layers in terms of cellular morphology, function, and connectivity, is not fully understood. There are numerous accounts in the literature that describe the compartmentalization of the rodent somatosensory cortex into its distinct whisker-related `hollow' and `septal' regions, referred to collectively as the barrel cortex. Cytoarchitecturally, the majority of excitatory neurons in layer 4 (L4) are of spiny stellate morphology, situated within the walls of barrel hollows, possessing asymmetrical dendritic fields that are oriented towards dense whisker-related thalamocortical axon (TCA) terminals. By contrast, pyramidal neurons in barrel cortex are associated with cell-sparse septa regions, receiving distinct inputs and are considered part of separate whisker-related circuits. Despite these differences, these barrel cell types cannot be separated on the basis of their electrophysiological properties, moreover, a detailed molecular characterization that underlies their diversity is lacking. In this study, we identified specific hollow- and septa-related patterns of reciprocal gene expression that hinted at possible roles in barrel formation/function. Further, a close spatiotemporal relationship between these expression patterns, cortical neuron morphology, and TCA innervation was observed over the first postnatal week, suggesting that extracortical inputs provide important cues to shape sensory cortical circuits. Disruption of neural activity within the pathway had little effect on the reciprocal expression of hollow- and septa-related genes. Profound changes in barrel marker expression, however, were induced by alterations in TCA innervation patterns. Together our results suggest a model whereby the default state of the developing neocortex is 'higher-order' in nature, upon which TCA-derived molecular cues are required to both turn on and restrict expression of hollow- and septa-related genes, respectively, leading to barrel formation and neuronal diversity of L4 neurons. | | 7月28日（日）10:15～10:45 第5会場（朱鷺メッセ 3F 302）
4S05m-4
Development of pulvino-cortical circuits: implications for behaviours and disorders.
James Andrew Bourne（Bourne James Andrew）
Australian Regenerative Medicine Institute, Monash University, Australia
The pulvinar is the largest collection of nuclei of the thalamus in primates, including humans, comprising 3 nuclei and further subdivisions. Even though it has been demonstrated to be embedded within sensory systems and connect with the majority of the neocortex, its function remains unclear. Over the past decade, my group have been instrumental in demonstrating in the marmoset monkey the role of the medial subdivision of the inferior pulvinar in the development of the dorsal stream visual cortex and the manifestations of a lesion to this region of the brain in early life. To this end, we now know that this area plays an implicit role in the development of the visual cortex and establishment of visuomotor behaviours, such as reaching and grasping. Furthermore, we have evidence that the pulvinar can route visual information to the visual cortex following a lesion of the geniculostriate pathway in early life in both monkeys and humans. Collectively, these data demonstrate an essential role for the inferior pulvinar thalamic nuclei in early life. Furthermore, up to this point, it was suggested that the thalamocortical circuits were `hardwired' by birth yet we now have evidence and an example of their inherent plastic nature early in life and ability to reroute sensory information. Our attention is now focussed on the other pulvinar nuclei, establishing how they may be operating to ensure appropriate motor and cognitive behaviours, and investigating their links to developmental diseases such as schizophrenia, where this early life plasticity may be aberrant. | |
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