Instructing Perisomatic Inhibition by Direct Lineage Reprogramming of Neocortical Projection Neurons

Neuron. 2015 Nov 4;88(3):475-83. doi: 10.1016/j.neuron.2015.10.006.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Corpus Callosum / cytology
  • Corpus Callosum / physiology*
  • Mice
  • Mice, Transgenic
  • Neocortex / cytology
  • Neocortex / physiology*
  • Nerve Net / cytology
  • Nerve Net / physiology*
  • Neural Inhibition / physiology*
  • Neural Pathways / cytology
  • Neural Pathways / physiology
  • Neurons / physiology*
  • Organ Culture Techniques