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

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Science  28 Oct 2016:
Vol. 354, Issue 6311, pp. 459-465
DOI: 10.1126/science.aaf2156

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Integration of adult-born brain cells

Physical exercise or exploration of a novel environment greatly influences the production, maturation, and connectivity of adult-born neurons. Alvarez et al. investigated how experience affects the incorporation of adult-born neurons into the hippocampal network. A brief period of sensory enrichment when new neurons were 9 to 10 days old led to neurons having larger dendrites and more functional spine synapses. A disynaptic preexisting feedback circuit promoted the growth and integration of the new cells.

Science, this issue p. 459

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.

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