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

TL;DR

This study shows that specific brain circuits in male mice influence social rank and anxiety, offering new insights into social behavior regulation.

Contribution

The study identifies glutamatergic neurons in the substantia nigra pars reticulata as key regulators of social hierarchy and anxiety in male mice.

Findings

Activation of SNrGlu neurons increases during effortful social behaviors in mice.

Optogenetic activation of SNrGlu neurons raises social rank, while inhibition lowers it.

Stimulation of SNrGlu terminals in the DRN reduces anxiety and elevates social status.

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 SNr glutamatergic (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 SNrGlu neurons induced upward or downward shifts in social ranks, respectively. Additionally, our findings indicate that the activation of SNr glutamatergic terminals in DRN elevates social status and reduces anxiety levels in mice. Collectively, these results broaden our understanding of the functions associated with SNrGlu neurons and underscore their critical role in regulating social hierarchy among male mice. This work enhances our understanding of the functions of SNrGlu neurons in both physiological contexts and neurological disorders.

The dorsal raphe nucleus in the brain is critical for establishing social rank, but the circuit is not fully understood. This study in male mice shows that glutamatergic projections from the substantia nigra pars reticulata to the dorsal raphe nucleus can regulate social rank and anxiety levels.

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