Distinct Dorsal and Ventral Hippocampal CA3 Outputs Govern Contextual Fear Discrimination.
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| Abstract | 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. |
| Year of Publication | 2020
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| Journal | Cell Rep
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| Volume | 30
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| Issue | 7
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| Pages | 2360-2373.e5
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| Date Published | 2020 Feb 18
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| ISSN | 2211-1247
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| DOI | 10.1016/j.celrep.2020.01.055
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| PubMed ID | 32075769
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