Instructing Perisomatic Inhibition by Direct Lineage Reprogramming of Neocortical Projection Neurons
Zhanlei Ye 5, Mohammed A. Mostajo-Radji 5, Juliana R. Brown, Caroline Rouaux 4, Giulio Srubek Tomassy, Takao K. Hensch correspondence email, Paola Arlotta correspondence email
4Present address: INSERM U1118, Mécanismes Centraux et Périphériques de la Neurodégénérescence, Faculté de Médecine, Université de Strasbourg, 67085 Strasbourg, France
5Co-first author
DOI: http://dx.doi.org/10.1016/j.neuron.2015.10.006
Source/Fonte: Extreme Tech
Highlights
•Reprogrammed cortical callosal neurons acquire identity traits of corticofugal neurons
•Induced corticofugal neurons receive increased input from PV+ cortical interneurons
•Projection neuron class-specific identity instructs afferent inhibitory connectivity
Summary
During development of the cerebral cortex, local GABAergic interneurons recognize and pair with excitatory projection neurons to ensure the fine excitatory-inhibitory balance essential for proper circuit function. Whether the class-specific identity of projection neurons has a role in the establishment of afferent inhibitory synapses is debated. Here, we report that direct in vivo lineage reprogramming of layer 2/3 (L2/3) callosal projection neurons (CPNs) into induced corticofugal projection neurons (iCFuPNs) increases inhibitory input onto the converted neurons to levels similar to that of endogenous CFuPNs normally found in layer 5 (L5). iCFuPNs recruit increased numbers of inhibitory perisomatic synapses from parvalbumin (PV)-positive interneurons, with single-cell precision and despite their ectopic location in L2/3. The data show that individual reprogrammed excitatory projection neurons extrinsically modulate afferent input by local PV+ interneurons, suggesting that projection neuron class-specific identity can actively control the wiring of the cortical microcircuit.
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