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Balancing tonic and phasic inhibition in hypothalamic corticotropin‐releasing hormone neurons
Author(s) -
Colmers Phillip L.W.,
Bains Jaideep S.
Publication year - 2018
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jp275588
Subject(s) - tonic (physiology) , gaba transporter , inhibitory postsynaptic potential , gabaa receptor , hypothalamus , corticotropin releasing hormone , neuroscience , gamma aminobutyric acid , postsynaptic potential , chemistry , neurotransmission , medicine , receptor , endocrinology , biology , gabaergic , biochemistry
Key points GABA transporter (GAT) blockade recruits extrasynaptic GABA A receptors (GABA A Rs) and amplifies constitutive presynaptic GABA B R activity. Extrasynaptic GABA A Rs contribute to a tonic current. Corticosteroids increase the tonic current mediated by extrasynaptic GABA A Rs.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 (GATs) 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 A R 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.