No evidence for sex differences in the electrophysiological properties and excitatory synaptic input onto nucleus accumbens shell medium spiny neurons

Abstract

Sex differences exist in how the brain regulates motivated behavior and reward, both in normal and pathological contexts. Investigations into the underlying neural mechanisms have targeted the striatal brain regions, including the dorsal striatum and nucleus accumbens core and shell. These investigations yield accumulating evidence of sexually different electrophysiological properties, excitatory synaptic input, and sensitivity to neuromodulator/hormone action in select striatal regions both before and after puberty. It is unknown whether the electrical properties of neurons in the nucleus accumbens shell differ by sex, and whether sex differences in excitatory synaptic input are present before puberty. To test the hypothesis that these properties differ by sex, we performed whole-cell patch clamp recordings on male and female medium spiny neurons (MSNs) in acute brain slices obtained from prepubertal rat nucleus accumbens shell. We analyzed passive and active electrophysiological properties, and miniature excitatory synaptic currents (mEPSC). No sex differences were detected; this includes those properties such as intrinsic excitability, action potential afterhyperpolarization, threshold, and mEPSC frequency that have been found to differ by sex in other striatal regions and/or developmental periods. These findings indicate that unlike other striatal brain regions, the electrophysiological properties of nucleus accumbens shell MSNs do not differ by sex. Overall, it appears that sex differences in striatal function, including motivated behavior and reward, are likely mediated by other factors and striatal regions.

Significance Statement: Genetic sex and steroid sex hormone exposure modulate striatal function. Sex differences in the electrophysiological properties of medium spiny neurons (MSNs), the principal striatal neuron type, have been identified in two striatal regions: the dorsal striatum and the nucleus accumbens core. The extent of sex differences in the third striatal region, the nucleus accumbens shell, is unclear. We tested whether MSN intrinsic electrophysiological properties and miniature excitatory synaptic currents (mEPSC) differ by sex. Our data support that nucleus accumbens shell MSN properties do not differ by sex. This study provides novel insight showing that the neurobiological mechanisms underlying sex differences in striatal function are likely mediated by other striatal regions and/or processes.