The estrous cycle and 17β‐estradiol modulate the electrophysiological properties of rat nucleus accumbens core medium spiny neurons

Abstract

The nucleus accumbens core is a key nexus within the mammalian brain for integrating the premotor and limbic systems and regulating important cognitive functions such as motivated behaviors. Nucleus accumbens core functions show sex differences and are sensitive to the presence of hormones such as 17β-estradiol (estradiol) in normal and pathological contexts. The primary neuron type of the nucleus accumbens core, the medium spiny neuron (MSN), exhibits sex differences in both intrinsic excitability and glutamatergic excitatory synapse electrophysiological properties. Here, we provide a review of recent literature showing how estradiol modulates rat nucleus accumbens core MSN electrophysiology within the context of the estrous cycle. We review the changes in MSN electrophysiological properties across the estrous cycle and how these changes can be mimicked in response to exogenous estradiol exposure. We discuss in detail recent findings regarding how acute estradiol exposure rapidly modulates excitatory synapse properties in nucleus accumbens core but not caudate-putamen MSNs, which mirror the natural changes seen across estrous cycle phases. These recent insights demonstrate the strong impact of sex-specific estradiol action upon nucleus accumbens core neuron electrophysiology.

Cocaine Exposure Increases Excitatory Synaptic Transmission and Intrinsic Excitability in the Basolateral Amygdala in Male and Female Rats and across the Estrous Cycle

“…A similar increase in miniature EPSC frequency but not amplitude and no change in the paired-pulse ratio of evoked EPSCs were also observed in NAcc medium spiny neurons following experimenter-delivered or non-contingent cocaine injections and several weeks of withdrawal in both male and female rats, with a more robust effect observed in females [33]. Studies in drug-naïve animals have also shown that estrous cycle fluctuations alone can influence neuronal physiology in different brain regions [34]. Indeed, we also observed an increase in sEPSC amplitude in estrus females that was independent of drug exposure (Fig.…”

Sex difference in the effect of environmental enrichment on food restriction-induced persistence of cocaine conditioned place preference and mechanistic underpinnings

“…Further, if DA is conserved during food restriction, and restoration of DA utilization by environmental enrichment is key to effects observed in males, the marked fluctuations in DA utilization and receptor density across stages of the estrous cycle [ 85 – 87 ] may create a ‘noisy’ background that obscures the effect of environmental enrichment. Additional mechanistic complication may arise from the variation in glutamate utilization, AMPA receptor expression [ 88 ], MSN intrinsic excitability, and amplitude and frequency of sEPSCs across phases of the estrous cycle [ 89 ].…”

ERα Stimulation Rapidly Modulates Excitatory Synapse Properties in Female Rat Nucleus Accumbens Core

“…Males and females express ERs and aromatase in adulthood; however, it is not known whether ERs and aromatase expression differ by sex or estrous cycle phase [102, 135]. Our original study found no difference in the sensitivity to rapid estradiol action upon mEPSC frequency between different estrous cycle phases; thus, we did not assess the estrous cycle as an experimental variable in this brief report.…”