Intrinsic excitability varies by sex in prepubertal striatal medium spiny neurons.

Sex differences in neuron electrophysiological properties were traditionally associated with brain regions directly involved in reproduction in adult, postpubertal animals. There is growing acknowledgement that sex differences can exist in other developmental periods and brain regions as well. This includes the dorsal striatum (caudate/putamen), which shows robust sex differences in gene expression, neuromodulator action (including dopamine and 17β-estradiol), and relevant sensorimotor behaviors and pathologies such as the responsiveness to drugs of abuse. Here we examine whether these sex differences extend to striatal neuron electrophysiology. We test the hypothesis that passive and active medium spiny neuron (MSN) electrophysiological properties in prepubertal rat dorsal striatum differ by sex. We made whole cell recordings from male and females MSNs from acute brain slices. The slope of the evoked firing rate to current injection curve was increased in MSNs recorded from females compared with males. The initial action potential firing rate was increased in MSNs recorded from females compared with males. Action potential after-hyperpolarization peak was decreased, and threshold was hyperpolarized in MSNs recorded from females compared with males. No sex differences in passive electrophysiological properties or miniature excitatory synaptic currents were detected. These findings indicate that MSN excitability is increased in prepubertal females compared with males, providing a new mechanism that potentially contributes to generating sex differences in striatal-mediated processes. Broadly, these findings demonstrate that sex differences in neuron electrophysiological properties can exist prepuberty in brain regions not directly related to reproduction.