Astrocytes close the mouse critical period for visual plasticity

Science. 2021 Jul 2;373(6550):77-81. doi: 10.1126/science.abf5273.

Abstract

Brain postnatal development is characterized by critical periods of experience-dependent remodeling of neuronal circuits. Failure to end these periods results in neurodevelopmental disorders. The cellular processes defining critical-period timing remain unclear. Here, we show that in the mouse visual cortex, astrocytes control critical-period closure. We uncover the underlying pathway, which involves astrocytic regulation of the extracellular matrix, allowing interneuron maturation. Unconventional astrocyte connexin signaling hinders expression of extracellular matrix-degrading enzyme matrix metalloproteinase 9 (MMP9) through RhoA-guanosine triphosphatase activation. Thus, astrocytes not only influence the activity of single synapses but also are key elements in the experience-dependent wiring of brain circuits.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astrocytes / metabolism
  • Astrocytes / physiology*
  • Connexin 30 / metabolism
  • Critical Period, Psychological*
  • Enzyme Activation
  • GTP Phosphohydrolases / metabolism
  • Interneurons / metabolism
  • Interneurons / physiology
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neuronal Plasticity*
  • Synapses / metabolism
  • Visual Cortex / growth & development*
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Connexin 30
  • Gjb6 protein, mouse
  • Matrix Metalloproteinase 9
  • Mmp9 protein, mouse
  • GTP Phosphohydrolases
  • RhoA protein, mouse
  • rhoA GTP-Binding Protein