Effects of progesterone nuclear receptor on dopaminergic nuclei involved in social aggression in zebrafish (Danio rerio)

Aggression is tightly controlled by hormonal and neural regulation in all social animals. Although extensive effort has been invested in studying the neuroendocrine bases of aggressive behavior, our knowledge of the role progesterone plays in regulating aggression remains poorly understood. This is because most research investigating progesterone function has been limited to female ovulation and reproduction. Recently, we demonstrated that progesterone nuclear receptor knockout (Pgr KO) male zebrafish display heightened aggression toward conspecifics compared to wildtype (WT) cohorts. However, the neurophysiological bases underlying this observation remained unknown. Here we examined morphological differences of brain nuclei associated in social aggression between Pgr KO and WT male zebrafish using the Tg(dat:EGFP) transgenic line. Progesterone and dopaminergic systems are tightly intertwined and Pgr is known to be expressed widely in hypothalamic dopaminergic neurons. We hypothesized that heightened aggression will be manifested morphologically in differences in the number of dopaminergic neurons in hypothalamic brain nuclei implicated in social regulation. To test this hypothesis, we measured the number of dopamine reuptake transporter (DAT) expressing neurons in the telencephalon and lateral recess (nuclei associated with aggression) and the pre-optic area and pretectum (nuclei associated with submissiveness). Results of confocal microscopy and automated quantification suggest a reduced number of DAT positive cells in the lateral recess of Pgr KO animals compared to control WTs\; while the number of cells in the telencephalon was higher in Pgr KO compared to WTs. Finally, results show no differences in the number of neurons in the preoptic area or pretectum between Pgr KO vs. WTs. Our results highlight the importance of Pgr in inducing morphological plasticity of brain nuclei associated in social aggression