期刊
BEHAVIOURAL BRAIN RESEARCH
卷 399, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.bbr.2020.112917
关键词
Adult neurogenesis; Dentate gyrus; CA3; Dorsolateral septum; c-Fos; Somatostatin
资金
- 2014 NARSAD Young Investigator Award
- Bettencourt-Schueller Foundation
- Philippe Foundation
- 2016 MGH ECOR Fund for Medical Discovery (FMD) Postdoctoral Fellowship Awards
- US National Institutes of Health Biobehavioral Research Awards for Innovative New Scientists (BRAINS) [1-R01MH104175]
- NIH-NIA [1R01AG048908-01A1]
- NIH [1R01MH111729-01]
- NINDS [R56NS117529]
- James and Audrey Foster MGH Research Scholar Award
- Ellison Medical Foundation New Scholar in Aging
- Whitehall Foundation
- Inscopix Decode Award
- NARSAD Independent Investigator Award
- Blue Guitar Fund
- Harvard Neurodiscovery Center/MADRC Center Pilot Grant Award
- Alzheimer's Association research grant
- Harvard Stem Cell Institute (HSCI) Development grant
- HSCI seed grant
Enhancing adult hippocampal neurogenesis through genetic means has been shown to promote contextual fear discrimination by increasing c-Fos expression in specific subfields of the hippocampus. Additionally, activation of somatostatin expressing neurons in the dorsolateral septum indicates their role in calibrating defensive behavior, providing insights into how this genetic enhancement affects hippocampal-dorsolateral septal circuits.
Hippocampal circuitry is continuously modified by integration of adult-born dentate granule cells (DGCs). Prior work has shown that enhancing adult hippocampal neurogenesis decreases interference or overlap or conflict between ensembles of similar contexts and promotes discrimination of a shock-associated context from a similar, neutral context. However, the impact of enhanced integration of adult-born neurons on hippocampal network activity or downstream circuits such as the dorsolateral septum that mediate defensive behavioral responses is poorly understood. Here, we first replicated our finding that genetic expansion of the population of adult-born dentate granule cells (8 weeks and younger) promotes contextual fear discrimination. We found that enhanced contextual fear discrimination is associated with greater c-Fos expression in discrete hippocampal subfields along the proximo-distal and dorsoventral axis. Examination of the dorsolateral septum revealed an increase in activation of somatostatin expressing neurons consistent with recent characterization of these cells as calibrators of defensive behavior. Together, these findings begin to shed light on how genetically enhancing adult hippocampal neurogenesis affects activity of hippocampal-dorsolateral septal circuits.
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