The organization and development of cortical interneuron presynaptic circuits are area specific

Cell Rep. 2021 Nov 9;37(6):109993. doi: 10.1016/j.celrep.2021.109993.

Abstract

Parvalbumin and somatostatin inhibitory interneurons gate information flow in discrete cortical areas that compute sensory and cognitive functions. Despite the considerable differences between areas, individual interneuron subtypes are genetically invariant and are thought to form canonical circuits regardless of which area they are embedded in. Here, we investigate whether this is achieved through selective and systematic variations in their afferent connectivity during development. To this end, we examined the development of their inputs within distinct cortical areas. We find that interneuron afferents show little evidence of being globally stereotyped. Rather, each subtype displays characteristic regional connectivity and distinct developmental dynamics by which this connectivity is achieved. Moreover, afferents dynamically regulated during development are disrupted by early sensory deprivation and in a model of fragile X syndrome. These data provide a comprehensive map of interneuron afferents across cortical areas and reveal the logic by which these circuits are established during development.

Keywords: ALM; GABAergic interneurons; cortical areas; development; fragile X syndrome; monosynaptic rabies tracing; sensory cortex; thalamocortical input.

Publication types

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

MeSH terms

  • Animals
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology*
  • Female
  • Fragile X Mental Retardation Protein / physiology*
  • Fragile X Syndrome / genetics
  • Fragile X Syndrome / metabolism
  • Fragile X Syndrome / pathology*
  • Interneurons / metabolism
  • Interneurons / pathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neural Pathways
  • Presynaptic Terminals / metabolism
  • Presynaptic Terminals / pathology*
  • Rabies virus / genetics
  • Sense Organs / metabolism
  • Sense Organs / pathology*
  • Synapses / metabolism
  • Synapses / pathology*

Substances

  • Fmr1 protein, mouse
  • Fragile X Mental Retardation Protein