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Neuron DOI:10.1016/j.neuron.2015.10.006

Instructing Perisomatic Inhibition by Direct Lineage Reprogramming of Neocortical Projection Neurons.

Publication TypeJournal Article
Year of Publication2015
AuthorsYe, Z, Mostajo-Radji, MA, Brown, JR, Rouaux, C, Tomassy, GSrubek, Hensch, TK, Arlotta, P
Date Published2015 Nov 04
KeywordsAnimals, Corpus Callosum, Mice, Mice, Transgenic, Neocortex, Nerve Net, Neural Inhibition, Neural Pathways, Neurons, Organ Culture Techniques

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.


Alternate JournalNeuron
PubMed ID26539889
PubMed Central IDPMC4794746
Grant ListR01 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