Dataset Information

A circuit from dorsal hippocampal CA3 to parvafox nucleus mediates chronic social defeat stress-induced deficits in preference for social novelty.

ABSTRACT: The preference for social novelty is crucial to the social life of humans and rodents. However, the neural mechanisms underlying social novelty preference are poorly understood. Here, we found that chronic social defeat stress (CSDS) reduced the preference for social novelty in mice by impairing the response of CaMKIIα⁺ neurons in the CA3 region of dorsal hippocampus (dCA3) during approach to an unfamiliar mouse. The deficits of social novelty preference in CSDS-treated mice were reversed by activating the output from dCA3 to the GABAergic neurons in the lateral septum (LS). The activation of GABAergic projection from LS recruited a circuit that inhibited the Foxb1⁺ neurons in the parvafox nucleus (PFN), which drove social avoidance by projecting to the lateral periaqueductal gray (lPAG). These results suggest that a previously unidentified circuit of dCA3^CaMKIIα+→LS^GABA+→PFN^Foxb1+→lPAG mediates the deficits of social novelty preference induced by CSDS.

SUBMITTER: Liu Y

PROVIDER: S-EPMC8865774 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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A circuit from dorsal hippocampal CA3 to parvafox nucleus mediates chronic social defeat stress-induced deficits in preference for social novelty.

Liu Yang Y Deng Si-Long SL Li Liang-Xia LX Zhou Zi-Xiang ZX Lv Qiu Q Lv Qiu Q Wang Zhong-Yuan ZY Wang Fang F Chen Jian-Guo JG

Science advances 20220223 8

The preference for social novelty is crucial to the social life of humans and rodents. However, the neural mechanisms underlying social novelty preference are poorly understood. Here, we found that chronic social defeat stress (CSDS) reduced the preference for social novelty in mice by impairing the response of CaMKIIα<sup>+</sup> neurons in the CA3 region of dorsal hippocampus (dCA3) during approach to an unfamiliar mouse. The deficits of social novelty preference in CSDS-treated mice were reve ...[more]

PMID: 35196094

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Project description:A key mode of neuronal communication between distant brain regions is through excitatory synaptic transmission mediated by long-range glutamatergic projections emitted from principal neurons. The long-range glutamatergic projection normally forms numerous en passant excitatory synapses onto both principal neurons and interneurons along its path. Under physiological conditions, the monosynaptic excitatory drive onto postsynaptic principal neurons outweighs disynaptic feedforward inhibition, with the net effect of depolarizing principal neurons. In contrast with this conventional doctrine, here we report that a glutamatergic projection from the hypothalamic supramammillary nucleus (SuM) largely evades postsynaptic pyramidal neurons (PNs), but preferentially target interneurons in the hippocampal CA3 region to predominantly provide feedforward inhibition. Using viral-based retrograde and anterograde tracing and ChannelRhodopsin2 (ChR2)-assisted patch-clamp recording in mice of either sex, we show that SuM projects sparsely to CA3 and provides minimal excitation onto CA3 PNs. Surprisingly, despite its sparse innervation, the SuM input inhibits all CA3 PNs along the transverse axis. Further, we find that SuM provides strong monosynaptic excitation onto CA3 parvalbumin-expressing interneurons evenly along the transverse axis, which likely mediates the SuM-driven feedforward inhibition. Together, our results demonstrate that a novel long-range glutamatergic pathway largely evades principal neurons, but rather preferentially innervates interneurons in a distant brain region to suppress principal neuron activity. Moreover, our findings reveal a new means by which SuM regulates hippocampal activity through SuM-to-CA3 circuit, independent of the previously focused projections from SuM to CA2 or dentate gyrus.SIGNIFICANCE STATEMENT The dominant mode of neuronal communication between brain regions is the excitatory synaptic transmission mediated by long-range glutamatergic projections, which form en passant excitatory synapses onto both pyramidal neurons and interneurons along its path. Under normal conditions, the excitation onto postsynaptic neurons outweighs feedforward inhibition, with the net effect of depolarization. In contrast with this conventional doctrine, here we report that a glutamatergic input from hypothalamic supramammillary nucleus (SuM) largely evades PNs but selectively targets interneurons to almost exclusively provide disynaptic feedforward inhibition onto hippocampal CA3 PNs. Thus, our findings reveal a novel subcortical-hippocampal circuit that enables SuM to regulate hippocampal activity via SuM-CA3 circuit, independent of its projections to CA2 or dentate gyrus.

Dataset Information

A circuit from dorsal hippocampal CA3 to parvafox nucleus mediates chronic social defeat stress-induced deficits in preference for social novelty.

Publications

A circuit from dorsal hippocampal CA3 to parvafox nucleus mediates chronic social defeat stress-induced deficits in preference for social novelty.

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