Journal
CELL REPORTS
Volume 30, Issue 7, Pages 2360-2373Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2020.01.055
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Funding
- 2014 NARSAD Young Investigator Award
- Bettencourt Schueller Foundation
- Philippe Foundation
- 2016 MGH ECOR Fund for Medical Discovery (FMD) Postdoctoral Fellowship Awards
- NIH [R01MH104175, R01AG048908, 1R01MH111729]
- James and Audrey Foster MGHResearch Scholar Award
- Ellison Medical Foundation New Scholar in Aging
- Whitehall Foundation
- Inscopix Decode award
- NARSAD Independent Investigator Award
- Ellison Family Philanthropic support
- Blue Guitar Fund
- Harvard Neurodiscovery Center-MADRC Center Pilot Grant award
- Alzheimer's Association Research Grant
- Harvard Stem Cell Institute Development grant
- HSCI seed grant
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Considerable work emphasizes a role for hippocampal circuits in governing contextual fear discrimination. However, the intra- and extrahippocampal pathways that route contextual information to cortical and subcortical circuits to guide adaptive behavioral responses are poorly understood. Using terminal-specific optogenetic silencing in a contextual fear discrimination learning paradigm, we identify opposing roles for dorsal CA3-CA1 (dCA3-dCA1) projections and dorsal CA3-dorsolateral septum (dCA3-DLS) projections in calibrating fear responses to certain and ambiguous contextual threats, respectively. Ventral CA3-DLS (vCA3-DLS) projections suppress fear responses in both certain and ambiguous contexts, whereas ventral CA3-CA1 (vCA3-vCA1) projections promote fear responses in both these contexts. Lastly, using retrograde monosynaptic tracing, ex vivo electrophysiological recordings, and optogenetics, we identify a sparse population of DLS parvalbumin (PV) neurons as putative relays of dCA3-DLS projections to diverse subcortical circuits. Taken together, these studies illuminate how distinct dCA3 and vCA3 outputs calibrate contextual fear discrimination.
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