Distinct Dorsal and Ventral Hippocampal CA3 Outputs Govern Contextual Fear Discrimination

被引：52

作者：

Besnard, Antoine ^{[1
,2
,3
]}

Miller, Samara M. ^{[1
,2
,3
]}

Sahay, Amar ^{[1
,2
,3
,4
]}

机构：

[1] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA

[2] Harvard Stem Cell Inst, Cambridge, MA 02138 USA

[3] Harvard Med Sch, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02114 USA

[4] BROAD Inst Harvard & MIT, Cambridge, MA 02142 USA

来源：

CELL REPORTS | 2020年 / 30卷 / 07期

关键词：

PATTERN SEPARATION; DENTATE GYRUS; NMDA RECEPTORS; LATERAL SEPTUM; MEMORY; CIRCUIT; COMPLETION; INHIBITION; ANXIETY; AXIS;

D O I：

10.1016/j.celrep.2020.01.055

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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.

引用

页码：2360 / 2373

页数：14

共 65 条

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