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The developmental genetic trajectories underlying the generation of GABAergic interneurons| old_uid | 16894 |
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| title | The developmental genetic trajectories underlying the generation of GABAergic interneurons |
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| start_date | 2018/12/03 |
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| schedule | 11h |
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| online | no |
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| details | invited by R. Cossart |
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| summary | Fundamental to understanding brain function is gaining an appreciation of how it is assembled. Inhibitory interneurons display a remarkable degree of heterogeneity and play an integral role in shaping the flow of information through all brain areas. Work from my laboratory over the past decade has sought to understand both how interneuron diversity is generated and how various interneuron subtypes become precisely embedded in the broad swath of circuits in which they are required. We have proposed a working model of how this is achieved that involves a initial step where “Cardinal” classes of interneurons are genetically specified into a relatively small number of subtypes, which possess common intrinsic properties, morphologies and propensities as to the cell types (i.e. excitatory vs inhibitory) and subcellular compartments (i.e. dendritic, somal, axonal) that they innervate. Cardinal specification, which we posit is determined upon interneurons become postmitotic, is followed by “Definitive” specification. Recent support for the existence of Cardinal identities has come from our efforts in applying massively parallel single-cell RNA-seq to profile the transcriptomes of interneurons spanning from their generation from naïve progenitors to take on four distinct cardinal identities. During their subsequent migration they further diversify into 10 distinct interneuron subtypes by the time they settle within the cerebral cortex. This second step we believe occurs post-migration when interneurons have attained their final position within the brain and is characterized by local cues including activity and trophic signals impinging on immature neurons to determine their appropriate and precise afferent and efferent connectivity within given brain regions. In this presentation, I will discuss recent work from my laboratory that supports this model. |
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| responsibles | Bernier |
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