Instructing Perisomatic Inhibition by Direct Lineage Reprogramming of Neocortical Projection Neurons.
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Abstract | 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. |
Year of Publication | 2015
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Journal | Neuron
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Volume | 88
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Issue | 3
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Pages | 475-83
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Date Published | 2015 Nov 04
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ISSN | 1097-4199
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DOI | 10.1016/j.neuron.2015.10.006
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PubMed ID | 26539889
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PubMed Central ID | PMC4794746
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Grant list | R01 NS062849 / NS / NINDS NIH HHS / United States
R01 NS078164 / NS / NINDS NIH HHS / United States
R01NS062849 / NS / NINDS NIH HHS / United States
R01NS078164 / NS / NINDS NIH HHS / United States
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