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Hypothalamic-amygdala gating of caregiving-like prosocial behavior in mice
Kai-Wen Geng, Rui-Rui Wang, Yan Yang, Yan Wang, Ting He, Chun-Li Li, Chong-Shun Xu, Jun Chen
Kai-Wen Geng, Rui-Rui Wang, Yan Yang, Yan Wang, Ting He, Chun-Li Li, Chong-Shun Xu, Jun Chen
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Research Article Cell biology Neuroscience

Hypothalamic-amygdala gating of caregiving-like prosocial behavior in mice

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Abstract

Distress sharing within an ingroup instinctively motivates caregiving-like prosocial behavior in social animals and humans, yet how aversive social stimuli paradoxically trigger such behavior remains unclear. Here, we show that stress-state matching in observer mice elicits caregiving-like behaviors (allogrooming and injury-targeted allolicking) toward cagemates in pain, resulting in synchronized social buffering. Importantly, we identify that the excitation of vasopressin receptor 1a–expressing (V1aR-expressing) neurons in the central medial amygdala (CeM) underlies both emotional-state matching and subsequent allogrooming/allolicking. This excitation is accomplished by arginine vasopressin (AVP) release from presynaptic terminals of the hypothalamic paraventricular nucleus (PVN) to act specifically on postsynaptic V1aR in the CeM. The CeMV1aR neurons then project to the ventral tegmental area (VTA) to drive caregiving-like actions through positive reinforcement, manifested as prosocial preference and recurrent allogrooming/allolicking, and to produce anxiolysis in the caregiver. Collectively, we unravel a dedicated trisynaptic PVNAVP-CeMV1aR-VTA circuit driving and gating caregiving-like behaviors and advance the mechanistic understanding of AVP-V1aR signaling in prosociality.

Authors

Kai-Wen Geng, Rui-Rui Wang, Yan Yang, Yan Wang, Ting He, Chun-Li Li, Chong-Shun Xu, Jun Chen

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Figure 3

The calcium dynamics of CeMV1aR neurons during different behavioral states.

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The calcium dynamics of CeMV1aR neurons during different behavioral stat...
(A) Targeting strategy for generating V1aRiCre knock-in mouse line. (B) Genotyping confirmation of wild-type and iCre positive mice. (C and D) Expression patterns (C) and coexpressing analysis (D) of V1aR mRNA and iCre mRNA in the CeM of V1aRiCre mice. (E) Schematic of viral injection, fiber implantation, and jGCaMP7s expression in the CeM. (F) Schematic of fiber photometry recording during social interaction. (G) Continuous Ca2+ signals of V1aRjGCaMP7s neurons during the initial social investigation (yellow shadowed), allogrooming (blue shadowed) and allolicking (pink shadowed). (H–J) Heatmaps (H), average traces (I), and mean ΔF/F (J) showing Ca2+ dynamics of V1aRjGCaMP7s neurons in response to naive and melittin-treated cagemates. (K–M and N–P) Heatmaps (K and N), average traces (L and O), and mean ΔF/F (M and P) showing Ca2+ dynamics of V1aRjGCaMP7s neurons before (baseline) and during allogrooming (K–M) or allolicking (N–P) episodes. (Q) Comparison of mean ΔF/F Ca2+ signals in V1aRjGCaMP7s neurons during allogrooming and allolicking episodes. (R–T) Heatmap (R), average trace (S), and mean ΔF/F (T) showing Ca2+ dynamics of V1aRjGCaMP7s neurons before (baseline) and during self-grooming episodes. Scale bars: 100 μm (original in C and E), 50 μm (magnified in C). Data are mean ± SEM. All mice are male. n = 3 mice in D; n = 12 or 17 trials from 7 mice in H–J; n = 25 trials from 5 mice in K–M; n = 11 trials from 5 mice in N–P; n = 16 trials from 5 mice in R–T. Statistical results are included in Supplemental Table 2. Mann Whitney U test for J and Q; Wilcoxon matched-pairs test for M and T; Paired t test for P.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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