Manipulation of radixin phosphorylation in the nucleus accumbens core modulates risky choice behavior

Abstract

Ezrin-Radixin-Moesin (ERM) proteins are actin-binding proteins that contribute to morphological changes in dendritic spines. Despite their significant role in regulating spine structure, the role of ERM proteins in the nucleus accumbnes (NAcc) is not well known, especially in in the context of risk-reward decision-making. Here, we measured the relationship between synaptic excitation and inhibition (E/I ratio) from medium spiny neurons in the NAcc core obtained in the rat after a rat gambling task (rGT). Then, after surgery of a phosphomimetic pseudo-active mutant form of radixin (Rdx-T564D) in the NAcc core, we examined its role in synaptic plasticity and the accompanying risk-choice behavior in rGT. We found that basal E/I ratio in the NAcc core was higher in risk-averse rats than risk-seeking rats. However, it was significantly reduced in risk-averse rats similar to that in risk-seeking rats in the presence of Rdx-T564D in the NAcc core. Furthermore, the head sizes of spines were shifted in risk-averse rats expressing Rdx-T564D in the NAcc core, similar to those observed in risk-seeking rats. The effects of Rdx-T564D in risk-averse rats were again manifested as behavioral changes, with reduced selection of optimal choices and increased selection of disadvantageous ones. In this study, we demonstrated that manipulation of radixin phosphorylation status in the NAcc core can alter glutamatergic synaptic transmission and spine structure at this site, as well as risk choice behaviors in the rGT. These novel findings illustrate that radixin in the NAcc core plays a significant role in determining risk preference during the rGT.