Balancing tonic and phasic inhibition in hypothalamic corticotropin releasing hormone neurons

Abstract

Corticotropin releasing hormone (CRH) neurons in the paraventricular nucleus of the hypothalamus (PVN) are integratory hubs that regulate the endocrine response to stress. GABA inputs provide a basal inhibitory tone that constrains this system and circulating glucocorticoids (CORT) are important feedback controllers of CRH output. Surprisingly little is known about the direct effects of CORT on GABA synapses in PVN. Here we used whole-cell patch clamp recordings from CRH neurons in mouse hypothalamic brain slices to examine the effects of CORT on synaptic and extrasynaptic GABA signalling. We show that GABA transporters (GAT) limit constitutive activation of presynaptic GABA_B receptors and ensure high release probability at GABA synapses. GATs, in combination with GABA_B receptors also curtail extrasynaptic GABA_AR signalling. CORT has no effect on synaptic GABA signalling, but increases extrasynaptic GABA tone through upregulation of postsynaptic GABA_A receptors. These data show that efficient GABA clearance and autoinhibition control the balance between synaptic (phasic) and extrasynaptic (tonic) inhibition in PVN CRH neurons. This balance is shifted towards increased extrasynaptic inhibition by CORT.

This article is protected by copyright. All rights reserved

from Physiology via xlomafota13 on Inoreader http://ift.tt/2Bi4oVm
via IFTTT