主题：Making up your mind: the developmental genetic trajectories resulting in the emergence of GABAergic interneuron identities.

报告人：

Prof. Gord Fishell,

Harvard Medical School, Department of Neurobiology, Boston MA, USA

Broad Institute, Stanley Center for Psychiatric Research, Cambridge MA, USA

时间：2019年3月26日，13:00-15:00

地点：北京大学金光生命大楼邓佑才报告厅

摘要：

Fundamental to understanding brain function is gaining an appreciation of how the it is assembled. In humans the cerebral cortex represents the center of consciousness, whose function depends upon a highly controlled balance of excitatory and inhibitory signaling.  Inhibitory neurons, while they in and of themselves do not create information, sculpt patterns of cortical activity, allowing for the coordination and selection of cognitive function and attention. Central to their ability to achieve this, inhibitory interneurons display a remarkable degree of heterogeneity.  Work from my laboratory over the past decade has sought to understand both how interneuron diversity is generated1-4 and how various interneuron subtypes become precisely embedded in the broad swath of circuits in which they are required5-7.  We have proposed a working model of how this is achieved that involves an initial step where “Cardinal” classes of interneurons are genetically specified into a relatively small number of subtypes8, 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.  To explore when interneurons become specified we have recently published a longitudinal single cell analysis tracking the emergence of interneuronal subtypes during development9.  Cardinal specification appears to be bestowed upon interneurons when they become postmitotic, with the emergence of the fundamental cardinal classes, demarcating the four fundamental modes of inhibition, feedforward (e.g. PV basket cells), feedback (e.g. SST Martinotti cells), disinhibition (e.g. VIP bipolar cells) and volume transport (e.g. Id2 neurogliaform cells).  Cardinal specification is refined upon interneurons reaching their settling positions within the brain, upon which the full repertoire of inhibitory subtypes is revealed.  We refer to this process as “State Association”.  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 activity5,6 and trophic signals10-12 impinging on immature neurons to determine their, survival, maturation and appropriate afferent and efferent connectivity within given brain regions.  Conversely, interneurons contribute to the emergence of brain function by forming developmental scaffolds that establish a balance between “bottom-up” and recurrent activity within the developing cortex7   

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2. Butt et al. Neuron 2008; 59:722-732.

3. Miyoshi et al. J Neuroscience 2007: 27:7786-7798.

4. Miyoshi et al. J Neuroscience 2010; 30:1582-1594

5. De Marco García et al. Nature 2011; 472:351-355.

6. De Marco García et al. Nat Neurosci. 2015; 18:393-401.

7. Tuncdemir et al.. Neuron 2016; 89:521-535.

8. Kepecs A, Fishell G.. Nature 2014; 505:318-326. 

9. Mayer et al. Nature, 2018; 2018 555: 457-462.

10. Quattrocolo et al. Cell Reports 2017 21:721-731.

11. Priya et al. Cell Reports, 2018 22:1695-1709.

12. Jaglin et al., Neuron 2018 (submitted)

邀请人：饶毅 教授、李毓龙 研究员