Aggressive experience increases PSD-95 in the nucleus accumbens of female hamsters via the fragile X mental retardation protein signaling pathway — ASN Events

Aggressive experience increases PSD-95 in the nucleus accumbens of female hamsters via the fragile X mental retardation protein signaling pathway (#136)

Kelsey M Moore 1 , Laura E Been 1 , Robert L Meisel 1
  1. Department of Neuroscience, University of Minnesota, Minneapolis, MN, United States

Aggression is a natural component of many social interactions in higher-order animals. Despite this behavior’s key influence on social structure across species, studies and knowledge of the mechanisms underlying aggressive behaviors, particularly among females, are lacking. It is known that the nucleus accumbens (NAc) plays a key role in aggressive responding in male rodents.We recently discovered that aggressive experience increases dendritic spine density on medium spiny neurons in the NAc of female hamsters, suggesting that the NAc of both females and males may be an integral brain region for modulating plasticity associated with prior aggressive experience. To investigate the mechanisms underlying these phenomena, we examined gene and protein expression of the synaptic scaffolding protein PSD-95, as well as fragile X mental retardation protein (FMRP), a signaling protein that modulates spine formation. We hypothesized that aggressive experience activates metabotropic glutamate receptor 5 (mGluR5), resulting in decreased phosphorylation of FMRP and subsequent formation of dendritic spines, as measured by increased expression of spine scaffolding proteins, such as PSD-95, in the NAc. Here we demonstrate that animals sacrificed 5 minutes following their last aggressive experience show transiently decreased phosphorylated FMRP that returns to baseline levels by 15 minutes. Further, animals sacrificed 1 week after their fifth aggressive experience demonstrated increased PSD-95 gene expression as well as a corresponding increase in PSD-95 protein levels in the NAc. A similar pattern of increased PSD-95 expression was seen in a separate cohort of male subjects, suggesting a common mechanism for escalated aggression in both sexes.  Interestingly, preliminary findings using a selective mGluR5 antagonist (MPEP) prevented the increases in PSD-95 gene expression and diminished the escalation of aggressive behavior across repeated experiences. These results suggest that the FMRP pathway is, at least in part, regulating synaptic plasticity in the NAc of female hamsters following aggressive experience.