Premium
Activation of astrocytic PAR1 receptors in the rat nucleus of the solitary tract regulates breathing through modulation of presynaptic TRPV1
Author(s) -
Huda Rafiq,
Chang Zheng,
Do Jeehaeh,
McCrimmon Donald R.,
Martina Marco
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/jp275127
Subject(s) - trpv1 , long term potentiation , neuroscience , neurotransmission , solitary tract , glutamate receptor , chemistry , microbiology and biotechnology , biology , receptor , nucleus , transient receptor potential channel , biochemistry
Key points In the rat nucleus of the solitary tract (NTS), activation of astrocytic proteinase‐activated receptor 1 (PAR1) receptors leads to potentiation of neuronal synaptic activity by two mechanisms, one TRPV1‐dependent and one TRPV1‐independent. PAR1‐dependent activation of presynaptic TRPV1 receptors facilitates glutamate release onto NTS neurons. The TRPV1‐dependent mechanism appears to rely on astrocytic release of endovanilloid‐like molecules. A subset of NTS neurons excited by PAR1 directly project to the rostral ventral respiratory group. The PAR1 initiated, TRPV1‐dependent modulation of synaptic transmission in the NTS contributes to regulation of breathing.Abstract Many of the cellular and molecular mechanisms underlying astrocytic modulation of synaptic function remain poorly understood. Recent studies show that G‐protein coupled receptor‐mediated astrocyte activation modulates synaptic transmission in the nucleus of the solitary tract (NTS), a brainstem nucleus that regulates crucial physiological processes including cardiorespiratory activity. By using calcium imaging and patch clamp recordings in acute brain slices of wild‐type and TRPV1 −/− rats, we show that activation of proteinase‐activated receptor 1 (PAR1) in NTS astrocytes potentiates presynaptic glutamate release on NTS neurons. This potentiation is mediated by both a TRPV1‐dependent and a TRPV1‐independent mechanism. The TRPV1‐dependent mechanism appears to require release of endovanilloid‐like molecules from astrocytes, which leads to subsequent potentiation of presynaptic glutamate release via activation of presynaptic TRPV1 channels. Activation of NTS astrocytic PAR1 receptors elicits cFOS expression in neurons that project to respiratory premotor neurons and inhibits respiratory activity in control, but not in TRPV1 −/− rats. Thus, activation of astrocytic PAR1 receptor in the NTS leads to a TRPV1‐dependent excitation of NTS neurons causing a potent modulation of respiratory motor output.