Department of Neurobiology, Brudnick Neuropsychiatric Research Institute University of Massachusetts Chan Medical School 364 Plantation St, LRB, Worcester, 01605, MA, USA.
Institute for Behavioral Genetics, University of Colorado Boulder 1480 30th St, Boulder, 80303, CO, USA.
Nat Commun. 2024 Apr 3;15(1):2891. doi: 10.1038/s41467-024-47255-y.
Animals are inherently motivated to explore social novelty cues over familiar ones, resulting in a novelty preference (NP), although the behavioral and circuit bases underlying NP are unclear. Combining calcium and neurotransmitter sensors with fiber photometry and optogenetics in mice, we find that mesolimbic dopamine (DA) neurotransmission is strongly and predominantly activated by social novelty controlling bout length of interaction during NP, a response significantly reduced by familiarity. In contrast, interpeduncular nucleus (IPN) GABAergic neurons that project to the lateral dorsal tegmentum (LDTg) were inhibited by social novelty but activated during terminations with familiar social stimuli. Inhibition of this pathway during NP increased interaction and bout length with familiar social stimuli, while activation reduced interaction and bout length with novel social stimuli via decreasing DA neurotransmission. These data indicate interest towards novel social stimuli is encoded by mesolimbic DA which is dynamically regulated by an IPN→LDTg circuit to control NP.
动物天生就有探索社会新奇线索的动机，而不是熟悉的线索，从而产生新奇偏好（NP），尽管 NP 的行为和电路基础尚不清楚。我们在小鼠中结合钙和神经递质传感器与光纤光度法和光遗传学，发现中脑边缘多巴胺（DA）神经传递强烈且主要由社会新奇所控制，控制 NP 期间的互动持续时间，这种反应因熟悉而显著降低。相比之下，投射到外侧背侧被盖核（LDTg）的脚间核（IPN）GABA 能神经元被社会新奇所抑制，但在与熟悉的社会刺激结束时被激活。在 NP 期间抑制这条通路会增加与熟悉的社会刺激的互动和持续时间，而激活则会通过减少 DA 神经传递来减少与新的社会刺激的互动和持续时间。这些数据表明，对新奇社会刺激的兴趣由中脑边缘 DA 编码，而 IPN→LDTg 回路对其进行动态调节以控制 NP。
