Sex differences in electrophysiological properties and voltage-gated ion channel expression in the paraventricular thalamic nucleus following repeated stress

Abstract

Background Habituation to repeated stress refers to a progressive reduction in the stress response following multiple exposures to the same, predictable stressor. We previously demonstrated that the posterior division of the paraventricular thalamic nucleus (pPVT) nucleus regulates habituation to 5 days of repeated restraint stress in male rats. Compared to males, female rats display impaired habituation to 5 days of restraint. To better understand how activity of pPVT neurons is differentially impacted in stressed males and females, we examined the electrophysiological properties of pPVT neurons under baseline conditions or following restraint. Methods Adult male and female rats were exposed to no stress (handling only), a single period of 30 min restraint or 5 daily exposures to 30 min restraint. 24 h later, pPVT tissue was prepared for recordings. Results We report here that spontaneous excitatory post-synaptic current (sEPSC) amplitude was increased in males, but not females, following restraint. Furthermore, resting membrane potential of pPVT neurons was more depolarized in males. This may be partially due to reduced potassium leakage in restrained males as input resistance was increased in male, but not female, rats 24 h following 1 or 5 days of 30-min restraint. Reduced potassium efflux during action potential firing also occurred in males following a single restraint as action potential half-width was increased following a single restraint. Restraint had limited effects on electrophysiological properties in females, although the mRNA for 10 voltage-gated ion channel subunits was altered in the pPVT of female rats. Conclusions The results suggest that restraint-induced changes in pPVT activation promote habituation in males. These findings are the first to describe a sexual dimorphism in stress-induced electrophysiological properties and voltage-gated ion channel expression in the pPVT. These results may explain, at least in part, why habituation to 5 days of restraint is disrupted in female rats.

The Paraventricular Thalamic Nucleus and Its Projections in Regulating Reward and Context Associations

“…Based on our findings and those of others, it is tempting to simplify the role of the PVT in reward processing by stating that when activated, the PVT evokes aversive behaviors and when inhibited, the PVT generates behaviors associated with positive reinforcement. However, reward processing encompasses a multitude of complex neural and behavioral functions that are regulated by the PVT, including arousal/wakefulness ( Gent et al, 2018 ; Ren et al, 2018 ; Wang et al, 2021 ; Eacret et al, 2023 ), stress ( Penzo et al, 2015 ; Öz et al, 2017 ; Bengoetxea et al, 2020 ; Dong et al, 2020 ; Yu et al, 2021 ; Corbett et al, 2022a , b ), learning and memory ( Hamlin et al, 2009 ; Li et al, 2011 ; Browning et al, 2014 ; Haight et al, 2015 ; Otis et al, 2017 , 2019 ; Keyes et al, 2020 ), prediction ( Munkhzaya et al, 2020 ), and reinforcement ( Marchant et al, 2010 ; Matzeu et al, 2015 ; Labouèbe et al, 2016 ; Zhang and van den Pol, 2017 ; Cheng et al, 2018 ; Giannotti et al, 2018 , 2021 ; Kuhn et al, 2018 ; Campus et al, 2019 ; Lafferty et al, 2020 ; Matzeu and Martin-Fardon, 2020 ; Chisholm et al, 2021 ; Kessler et al, 2021 ; Vollmer et al, 2022 ; Brown and Chaudhri, 2023 ). Therefore, it is more likely that the role of the PVT in reward processing is nuanced and multifaceted, depending upon the specific stage of reward learning, the type of reward (natural or drug-related), the PVT region (e.g., anterior, middle, posterior), the PVT cell type ( Gao et al, 2023 ), and the brain regions that the PVT interacts with.…”

A paraventricular thalamus to insular cortex glutamatergic projection gates “emotional” stress-induced binge eating in females

“…Of note, the same sex difference was not observed in insula [ 62 ]. Further, stress-induced electrophysiological changes in PVT neurons are observed in males but not females, providing a possible mechanism underlying the impairment in habituation to restraint stress observed in females [ 63 ]. Stress also differentially influences emotional perception in females versus males in relation to insula connectivity [ 64 ].…”