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Glutamatergic projections from the substantia nigra pars reticulata to the dorsal raphe nucleus regulate male social hierarchies

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Jun 12, 2025 version files 37.44 KB
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Abstract

Social hierarchy constitutes a fundamental organizational characteristic among various social species, significantly influencing individual survival, health, and reproductive success within these societies. Neurons in the substantia nigra pars reticulata (SNr) exhibit extensive connectivity with the dorsal raphe nucleus (DRN), a critical structure implicated in social interaction, reward processing, and the establishment of social rank. However, the specific neuronal types within the SNr, as well as the associated neural circuits that regulate social dominance, remain inadequately characterized. This study aims to elucidate the crucial role of SNrGlu neurons in the establishment and maintenance of social hierarchy in male mice. Employing fiber photometry, we observed that the activation of SNrGlu neurons increased during the initiation of effortful behaviors in the tube test. Further investigations revealed that optogenetic activation or chemogenetic inhibition of the glutamatergic neurons in the SNr induced upward or downward shifts in social ranks, respectively. Additionally, our findings indicate that the activation of SNr glutamatergic terminals in DRN elevated social status and reduces anxiety levels in mice. Collectively, these results broaden our understanding of the functions associated with SNr glutamatergic neurons and underscore their critical role in regulating social hierarchy among male mice. This work enhances our understanding of the functions of SNr glutamatergic neurons in both physiological contexts and neurological disorders.