Abstract
Recent evidence implicates adult hippocampal neurogenesis in regulating behavioral and physiologic responses to stress. Hippocampal neurogenesis occurs across the lifespan, however the rate of cell birth is up to 300% higher in adolescent mice compared to adults. Adolescence is a sensitive period in development where emotional circuitry and stress reactivity undergo plasticity establishing life-long set points. Therefore neurogenesis occurring during adolescence may be particularly important for emotional behavior. However, little is known about the function of hippocampal neurons born during adolescence. In order to assess the contribution of neurons born in adolescence to the adult stress response and depression-related behavior, we transiently reduced cell proliferation either during adolescence, or during adulthood in GFAP-Tk mice. We found that the intervention in adolescence did not change adult baseline behavioral response in the forced swim test, sucrose preference test or social affiliation test, and did not change adult corticosterone responses to an acute stressor. However following chronic social defeat, adult mice with reduced adolescent neurogenesis showed a resilient phenotype. A similar transient reduction in adult neurogenesis did not affect depression-like behaviors or stress induced corticosterone. Our study demonstrates that hippocampal neurons born during adolescence, but not in adulthood are important to confer susceptibility to chronic social defeat.
Highlights
Neurogenesis, the birth and integration of new neurons, occurs in the hippocampus across the lifespan
The number of cells dividing at the end of VGCV treatment that survived until P130 was reduced by 60% in glial fibrillary acidic protein (GFAP)-thymidine kinase (Tk)+/− mice compared to GFAPTk−/− littermate control mice (Figure 3A; t(29) = 3.258, p = 0.0029)
In adult mice the number of cells dividing at the end of VGCV treatment that survived until P130 was reduced by 75% in GFAP-Tk+/− mice compared to GFAP-Tk−/− littermate control mice (Figure 3D; t(26) = 5.125, p < 0.0001)
Summary
Neurogenesis, the birth and integration of new neurons, occurs in the hippocampus across the lifespan. Postnatal day 28 (P28) in mice, neurogenesis is restricted to the subgranular zone (SGZ) of the DG. During this time, newborn neurons populate the same anatomical space as cells born during adulthood, but at a considerably (up to 300%) higher rate (He and Crews, 2007). In adolescent and adult mice SGZ neural precursors differentiate into new neurons and functionally integrate into the granule cell layer (Toni et al, 2008). The process and localization of neurogenesis is homologous in adolescent and adult mice, the connectivity and functional contribution of new neurons may differ at these different stages of life (Wei et al, 2011)
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