Dopamine control of social novelty preference is constrained by an interpeduncular-tegmentum circuit

Susanna Molas (), Timothy G. Freels, Rubing Zhao-Shea, Timothy Lee, Pablo Gimenez-Gomez, Melanie Barbini, Gilles E. Martin and Andrew R. Tapper ()
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Susanna Molas: Brudnick Neuropsychiatric Research Institute University of Massachusetts Chan Medical School 364 Plantation St, LRB
Timothy G. Freels: Brudnick Neuropsychiatric Research Institute University of Massachusetts Chan Medical School 364 Plantation St, LRB
Rubing Zhao-Shea: Brudnick Neuropsychiatric Research Institute University of Massachusetts Chan Medical School 364 Plantation St, LRB
Timothy Lee: Brudnick Neuropsychiatric Research Institute University of Massachusetts Chan Medical School 364 Plantation St, LRB
Pablo Gimenez-Gomez: Brudnick Neuropsychiatric Research Institute University of Massachusetts Chan Medical School 364 Plantation St, LRB
Melanie Barbini: Brudnick Neuropsychiatric Research Institute University of Massachusetts Chan Medical School 364 Plantation St, LRB
Gilles E. Martin: Brudnick Neuropsychiatric Research Institute University of Massachusetts Chan Medical School 364 Plantation St, LRB
Andrew R. Tapper: Brudnick Neuropsychiatric Research Institute University of Massachusetts Chan Medical School 364 Plantation St, LRB

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-47255-y

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