Transient developmental imbalance of cortical interneuron subtypes presages long-term changes in behavior

Cell Rep. 2021 Jun 15;35(11):109249. doi: 10.1016/j.celrep.2021.109249.

Abstract

Cortical GABAergic interneurons are generated in large numbers in the ganglionic eminences and migrate into the cerebral cortex during embryogenesis. At early postnatal stages, during neuronal circuit maturation, autonomous and activity-dependent mechanisms operate within the cortex to adjust cell numbers by eliminating naturally occurring neuron excess. Here, we show that when cortical interneurons are generated in aberrantly high numbers-due to a defect in precursor cell proliferation during embryogenesis-extra parvalbumin interneurons persist in the postnatal mouse cortex during critical periods of cortical network maturation. Even though cell numbers are subsequently normalized, behavioral abnormalities remain in adulthood. This suggests that timely clearance of excess cortical interneurons is critical for correct functional maturation of circuits that drive adult behavior.

Keywords: Cux2; GABAergic interneurons; Pten; behavior; cortex; mouse; neurodevelopmental disorders; parvalbumin; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Behavior, Animal / physiology*
  • Cell Count
  • Cerebral Cortex / growth & development*
  • Homeodomain Proteins / metabolism
  • Interneurons / pathology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • PTEN Phosphohydrolase / metabolism
  • Parvalbumins / metabolism

Substances

  • Cux2 protein, mouse
  • Homeodomain Proteins
  • Parvalbumins
  • PTEN Phosphohydrolase