Activation of astrocytic PAR1 receptors in the rat nucleus of the solitary tract regulates breathing through modulation of presynaptic TRPV1

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 (PAR-1) 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 PAR-1 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 PAR-1 receptor in the NTS leads to a TRPV1-dependent excitation of NTS neurons causing a potent modulation of respiratory motor output.

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