Early cortical GABAergic interneurons determine the projection patterns of L4 excitatory neurons

Sci Adv. 2024 May 10;10(19):eadj9911. doi: 10.1126/sciadv.adj9911. Epub 2024 May 10.

Abstract

During cerebral cortex development, excitatory pyramidal neurons (PNs) establish specific projection patterns while receiving inputs from GABAergic inhibitory interneurons (INs). Whether these inhibitory inputs can shape PNs' projection patterns is, however, unknown. While layer 4 (L4) PNs of the primary somatosensory (S1) cortex are all born as long-range callosal projection neurons (CPNs), most of them acquire local connectivity upon activity-dependent elimination of their interhemispheric axons during postnatal development. Here, we demonstrate that precise developmental regulation of inhibition is key for the retraction of S1L4 PNs' callosal projections. Ablation of somatostatin INs leads to premature inhibition from parvalbumin INs onto S1L4 PNs and prevents them from acquiring their barrel-restricted local connectivity pattern. As a result, adult S1L4 PNs retain interhemispheric projections responding to tactile stimuli, and the mice lose whisker-based texture discrimination. Overall, we show that temporally ordered IN activity during development is key to shaping local ipsilateral S1L4 PNs' projection pattern, which is required for fine somatosensory processing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • GABAergic Neurons* / cytology
  • GABAergic Neurons* / metabolism
  • GABAergic Neurons* / physiology
  • Interneurons* / cytology
  • Interneurons* / metabolism
  • Interneurons* / physiology
  • Mice
  • Parvalbumins / metabolism
  • Pyramidal Cells / metabolism
  • Pyramidal Cells / physiology
  • Somatosensory Cortex* / cytology
  • Somatosensory Cortex* / metabolism
  • Somatosensory Cortex* / physiology

Substances

  • Parvalbumins