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

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 1

Stress coping and buffering nature of caregiving-like behavior in mice.

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Stress coping and buffering nature of caregiving-like behavior in mice. ...
(A) Left: a representative image of a mouse licking the injured right nape of its cagemate. Right: schematic of caregiving-like behavior test. (B and C) Time courses (B) and total durations (C) of allogrooming/allolicking toward naive, saline- and melittin-treated cagemates. (D) Proportions of allogrooming (AG) versus allolicking (AL) in total caregiving-like behavior toward pain-suffering cagemates. (E) Allogrooming/allolicking time toward melittin-treated demonstrators with or without bupivacaine (BPV) coinjection. (F) Schematic of divider paradigm followed by ELISA or caregiving-like behavior test. (G) Plasma CORT levels after 25–30 minutes social exposure to naive or melittin-treated demonstrator (with or without divider). (H) Observer allogrooming/allolicking duration toward melittin-treated cagemates: direct contact (no divider) versus reunion after 25–30 minutes divider separation (divider-reunion). (I) Allogrooming/allolicking time of observers pretreated with CRFR1 antagonist or saline toward pain-suffering cagemates. (J) Schematic of 2 consecutive caregiving-like behavior tests per observer. (K and L) Time courses (K) and total durations (L) of allogrooming/allolicking across 2 consecutive prosocial interactions. (M–P) Correlations between observers’ plasma CORT levels and duration of their allogrooming/allolicking (M), social investigation (N), huddling (O), and self-grooming (P) after 30-minute prosocial interactions. (Q) Correlation between demonstrators’ plasma CORT levels and received allogrooming/allolicking durations after 30-minute prosocial interactions. (R) Correlation between plasma CORT levels of observers and their demonstrators after 30-minute prosocial interaction. The control groups in E and H are the same dataset as the melittin group (first 30 minutes) in C. M–R, Solid lines, linear regression; dashed lines, 95% confidence intervals. B–E, G–I, K, L, mean ± SEM. All mice are male. Exact n values are indicated in the figure. AG, allogrooming; AL, allolicking; CRFR1, corticotropin-releasing factor receptor 1. 2. Brown-Forsythe and Welch ANOVA tests with Dunnett’s T3 multiple comparisons (1st 30 min) C; Kruskal-Wallis test with Dunn’s multiple comparisons (2nd 30 min) for C; Paired t test (Melittin, 1st vs 2nd) for C; Unpaired t test for E; 2-way ANOVA with Tukey’s multiple comparisons for G; Unpaired t test with Welch’s correction for H and I; Mann Whitney U test for L; Linear regression (Pearson correlation) for M, N, P; Linear regression (Spearman correlation) for O, Q, R.