Cellular mechanisms underlying social regulation of the posterior tubercular nucleus in zebrafish (Danio rerio)

Social status profoundly influences animal behavior through neural plasticity, yet the cellular mechanisms that mediate reconfiguration of neuromodulatory systems remain poorly understood. Here, we investigated status-dependent structural changes in the posterior tubercular nucleus (PTN) of adult zebrafish. Animals were assigned to four social conditions: communal, isolated, dominant, or subordinate. Using markers for cell proliferation (PCNA) and birth-dating (BrdU), we demonstrate that social dominance significantly enhances cell proliferation, leading to an increased population of PTN dopaminergic neurons. In contrast, subordinate and isolated fish exhibited suppressed proliferation and elevated expression of superoxide dismutase 1 (SOD1), suggesting that chronic social stress induces an oxidative burden that may lead to neuronal loss. Furthermore, we identified evidence of neurotransmitter phenotypic plasticity; subordinate fish displayed a significantly higher ratio of glutamatergic (vglut2a) to dopaminergic (dat) expression in PTN neurons compared to dominants, suggesting a status-dependent shift in neuromodulatory identity. Multivariate principal component analysis showed distinct neurobiological profiles that separate social ranks, suggesting that status-dependent plasticity is a coordinated multi-modal response whereby increased BrdU and PCNA expression clustered with the dominant profile while increased expression of cellular stress and shift to glutamate cellular identity clustered with social subordinate and isolate profiles. Collectively, our results improve our understanding of how social experience reshapes the zebrafish brain through integrated changes in cell proliferation, cellular shift in neurotransmitter identity and regulation of cellular viability; thus, providing a potential mechanism for the maintenance of stable behavioral phenotypes in competitive social environments.