Adolescent but not adult-born neurons are critical for susceptibility to chronic social defeat

Kirshenbaum, Greer S.; Lieberman, Sophie R.; Briner, Tamara J.; Leonardo, Eduardo David; Dranovsky, Alex

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.



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Frontiers in Behavioral Neuroscience

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February 26, 2015