This study investigated the neural circuit mechanisms underlying social novelty preference (NP) in mice. Using calcium and neurotransmitter sensors with fiber photometry and optogenetics, the researchers found that mesolimbic dopamine (DA) neurotransmission is strongly activated by social novelty, controlling the duration of social interaction. An interpeduncular nucleus (IPN) to lateral dorsal tegmentum (LDTg) circuit dynamically regulates this DA response. Inhibition of this IPN→LDTg pathway increased interaction with familiar stimuli, while activation reduced interaction with novel stimuli. These findings suggest that mesolimbic DA encodes interest in novel social stimuli, and this response is modulated by the IPN→LDTg circuit to control NP.

Susanna Molas, Timothy G. Freels, Rubing Zhao-Shea, Timothy Lee, Pablo Gimenez-Gomez, Melanie Barbini, Gilles E. Martin, Andrew R. Tapper