Sexually dimorphic characteristics of dopamine D1 receptor-expressing neurons within the shell of the nucleus accumbens of adolescent mice

Abstract

Abstract Background: Adolescence, a developmental stage, is characterized by psychosocial and biological changes. The nucleus accumbens (NAc), a striatal brain region composed of the core (NAcC) and shell (NAcSh), has been linked to risk-taking behavior and implicated in reward seeking and evaluation. Most neurons in the NAc are medium spiny neurons (MSNs) that express dopamine D1 receptors (D1R+) and/or dopamine D2 receptors (D2R+). Changes in dopaminergic and glutamatergic systems occur during adolescence and converge in the NAc. While there are previous investigations into sex differences in membrane excitability and synaptic glutamate transmission in both subdivisions of the NAc, to our knowledge, none have specified NAcSh D1R+MSNs from mice during mid-adolescence. Methods: Sagittal brain slices containing the NAc were prepared from B6.Cg-Tg(Drd1a-tdTomato)6Calak/J mice of both sexes from postnatal days 35-47. Stained smears were made from vaginal samples from female mice to identify the stage of Estrous at death. Whole-cell electrophysiology recordings were collected from NAcSh D1R+MSNs in the form of membrane-voltage responses to current injections and spontaneous excitatory postsynaptic currents (sEPSCs). Results: The action potential duration was longer in males than infemales. Additionally, the frequency of sEPSCs was higher in females, and the mean event amplitude was smaller than that in males. We found no evidence of the observed sex differences being driven by the stage of the Estrous cycle and no physiological parameter significantly varied with respect to the Estrous cycle. Conclusions: Taken together, our results indicate that NAcSh D1R+MSNs exhibit sex differences during mid-adolescence that are independent of the stage of Estrous, in both AP waveform and glutamate transmission, possibly due to changes in voltage-gated potassium channels and α-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors, respectively.