Vision-dependent specification of cell types and function in the developing cortex

Cell. 2022 Jan 20;185(2):311-327.e24. doi: 10.1016/j.cell.2021.12.022.

Abstract

The role of postnatal experience in sculpting cortical circuitry, while long appreciated, is poorly understood at the level of cell types. We explore this in the mouse primary visual cortex (V1) using single-nucleus RNA sequencing, visual deprivation, genetics, and functional imaging. We find that vision selectively drives the specification of glutamatergic cell types in upper layers (L) (L2/3/4), while deeper-layer glutamatergic, GABAergic, and non-neuronal cell types are established prior to eye opening. L2/3 cell types form an experience-dependent spatial continuum defined by the graded expression of ∼200 genes, including regulators of cell adhesion and synapse formation. One of these genes, Igsf9b, a vision-dependent gene encoding an inhibitory synaptic cell adhesion molecule, is required for the normal development of binocular responses in L2/3. In summary, vision preferentially regulates the development of upper-layer glutamatergic cell types through the regulation of cell-type-specific gene expression programs.

Keywords: binocular vision; cell types; critical period; inhibitory synapses; layer 2/3; single-nucleus RNA-seq; visual cortex.

Publication types

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

MeSH terms

  • Animals
  • Animals, Newborn
  • Biomarkers / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Glutamic Acid / metabolism
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Neurons / cytology
  • RNA-Seq
  • Transcriptome / genetics
  • Vision, Binocular / genetics
  • Vision, Ocular*
  • Visual Cortex / cytology*
  • Visual Cortex / embryology*
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Biomarkers
  • IgSF9b protein, mouse
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Glutamic Acid
  • gamma-Aminobutyric Acid