A disynaptic feedback network activated by experience promotes the integration of new granule cells

Science. 2016 Oct 28;354(6311):459-465. doi: 10.1126/science.aaf2156. Epub 2016 Oct 27.

Abstract

Experience shapes the development and connectivity of adult-born granule cells (GCs) through mechanisms that are poorly understood. We examined the remodeling of dentate gyrus microcircuits in mice in an enriched environment (EE). Short exposure to EE during early development of new GCs accelerated their functional integration. This effect was mimicked by in vivo chemogenetic activation of a limited population of mature GCs. Slice recordings showed that mature GCs recruit parvalbumin γ-aminobutyric acid-releasing interneurons (PV-INs) that feed back onto developing GCs. Accordingly, chemogenetic stimulation of PV-INs or direct depolarization of developing GCs accelerated GC integration, whereas inactivation of PV-INs prevented the effects of EE. Our results reveal a mechanism for dynamic remodeling in which experience activates dentate networks that "prime" young GCs through a disynaptic feedback loop mediated by PV-INs.

Publication types

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

MeSH terms

  • Animals
  • Dentate Gyrus / cytology
  • Dentate Gyrus / physiology*
  • Feedback, Physiological*
  • Female
  • Interneurons / cytology
  • Interneurons / metabolism
  • Interneurons / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Models, Neurological
  • Nerve Net / physiology*
  • Neurogenesis*
  • Neurons / cytology
  • Neurons / physiology*
  • Parvalbumins / metabolism
  • Social Environment
  • Synapses / physiology
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Parvalbumins
  • gamma-Aminobutyric Acid