Journal
HIPPOCAMPUS
Volume 28, Issue 10, Pages 735-744Publisher
WILEY
DOI: 10.1002/hipo.23008
Keywords
Adult hippocampal neurogenesis; contextual fear discrimination; memory; synaptic neurotransmission; time
Categories
Funding
- National Institute on Alcohol Abuse and Alcoholism [P50-AA022534]
- University of New Mexico Dedicated Health Research Funds
- NIGMS [1P20GM109089]
- NINDS [R21NS093442]
- NSF [7566685]
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [P20GM109089] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R21NS093442] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM [P50AA022534, R01AA017449] Funding Source: NIH RePORTER
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Adult neurogenesis is necessary for proper cognition and behavior, however, the mechanisms that underlie the integration and maturation of newborn neurons into the pre-existing hippocampal circuit are not entirely known. In this study, we sought to determine the role of action potential (AP)-dependent synaptic transmission by adult-generated dentate granule cells (DGCs) in their survival and function within the existing circuitry. We used a triple transgenic mouse (NestinCreER(T2):Snap25(fl/fl): tdTomato) to inducibly inactivate AP-dependent synaptic transmission within adult hippocampal progenitors and their progeny. Behavioral testing in a hippocampal-dependent A/B contextual fear-discrimination task revealed impaired discrimination learning in mice harboring SNAP-25-deficient adult-generated dentate granule cells (DGCs). Despite poor performance on this neurogenesis-dependent task, the production and survival of newborn DGCs was quantitatively unaltered in tamoxifen-treated NestinCreER(T2):Snap25(fl/fl): tdTomato SNAP compared to tamoxifen-treated NestinCreER(T2):Snap25(wt/wt): tdTomato control mice. Although SNAP-25-deficient adult DGCs displayed a small but statistically significant enhancement in proximal dendritic branching, their overall dendritic length and distal branching complexity was unchanged. SNAP-25-deficient newborn DGCs also displayed robust efferent mossy fiber output to CA3, with normal linear density of large mossy fiber terminals (LMTs). These studies suggest that AP-dependent neurotransmitter release by newborn DGCs is not essential for their survival or rudimentary structural maturation within the adult hippocampus.
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