GABAA receptor currents in the dorsal motor nucleus of the vagus in females: Influence of ovarian cycle and 5α-reductase inhibition

Erica L. Littlejohn, Liliana Espinoza, Monica M. Lopez, Bret N. Smith, Carie R. Boychuk

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

The dorsal motor nucleus of the vagus (DMV) contains the preganglionic motor neurons important in the regulation of glucose homeostasis and gastrointestinal function. Despite the role of sex in the regulation of these processes, few studies examine the role of sex and/or ovarian cycle in the regulation of synaptic neurotransmission to the DMV. Since GABAergic neurotransmission is critical to normal DMV function, the present study used in vitro whole cell patch-clamping to investigate whether sex differences exist in GABAergic neurotransmission to DMV neurons. It additionally investigated whether the ovarian cycle plays a role in those sex differences. The frequency of phasic GABAA receptor-mediated inhibitory postsynaptic currents in DMV neurons from females was lower compared with males, and this effect was TTX sensitive and abolished by ovariectomy (OVX). Amplitudes of GABAergic currents (both phasic and tonic) were not different. However, females demonstrated significantly more variability in the amplitude of both phasic and tonic GABAA receptor currents. This difference was eliminated by OVX in females, suggesting that these differences were related to reproductive hormone levels. This was confirmed for GABAergic tonic currents by comparing females in two ovarian stages, estrus versus diestrus. Female mice in diestrus had larger tonic current amplitudes compared with those in estrus, and this increase was abolished after administration of a 5α-reductase inhibitor but not modulation of estrogen. Taken together, these findings demonstrate that DMV neurons undergo GABAA receptor activity plasticity as a function of sex and/or sex steroids. NEW & NOTEWORTHY Results show that GABAergic signaling in dorsal vagal motor neurons (DMV) demonstrates sex differences and fluctuates across the ovarian cycle in females. These findings are the first to demonstrate that female GABAA receptor activity in this brain region is modulated by 5α-reductase-dependent hormones. Since DMV activity is critical to both glucose and gastrointestinal homeostasis, these results suggest that sex hormones, including those synthesized by 5α-reductase, contribute to visceral, autonomic function related to these physiological processes.

Original languageEnglish
Pages (from-to)2130-2141
Number of pages12
JournalJournal of Neurophysiology
Volume122
Issue number5
DOIs
StatePublished - 2019

Bibliographical note

Publisher Copyright:
Copyright © 2019 the American Physiological Society

Funding

This work was supported by American Heart Association Award SDG 16SDG26590000 to C. R. Boychuk and National Institutes of Health (NIH) Grants T32 HL-007446 to E. L. Littlejohn, R25 GM-095480-08 to L. Espi-noza, and R01 DK-056132 to B. N. Smith. The collection and analysis of serum estrogen and progesterone was also supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, NIH, through Grant UL1 TR-001998.

FundersFunder number
National Institutes of Health (NIH)T32 HL-007446, GM-095480-08
National Institutes of Health (NIH)
National Institute of Diabetes and Digestive and Kidney DiseasesR01DK056132
National Institute of Diabetes and Digestive and Kidney Diseases
National Center for Research Resources
American the American Heart AssociationSDG 16SDG26590000
American the American Heart Association
National Center for Advancing Translational Sciences (NCATS)UL1 TR-001998
National Center for Advancing Translational Sciences (NCATS)

    Keywords

    • Diestrus
    • Electrophysiology
    • GABA
    • Neurosteroid
    • Ovarian cycle
    • Vagus

    ASJC Scopus subject areas

    • General Neuroscience
    • Physiology

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