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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. [ABSTRACT FROM AUTHOR]

The nucleus of the solitary tract (NTS) is the major site for termination of visceral sensory afferents contributing to homeostatic regulation of, for example, arterial pressure, gastric motility, and breathing. Whereas much is known about how different neuronal populations influence these functions, information about the role of glia remains scant. In this article, we propose that glia may contribute to NTS functions by modulating excitatory neurotransmission. We found that acidification (pH 7.0) depolarizes NTS glia by inhibiting K+ -selective membrane currents. NTS glia also showed functional expression of voltagesensitive glutamate transporters, suggesting that extracellular acidification regulates synaptic transmission by compromising glial glutamate uptake. To test this hypothesis, we evoked glutamatergic slow excitatory potentials (SEPs) in NTS neurons with repetitive stimulation (20 pulses at 10 Hz) of the solitary tract. This SEP depends on accumulation of glutamate following repetitive stimulation, since it was potentiated by blocking glutamate uptake with DL-threo-benzyloxyaspartic acid (TBOA) or a glia-specific glutamate transport blocker, dihydrokainate (DHK). Importantly, extracellular acidification (pH 7.0) also potentiated the SEP. This effect appeared to be mediated through a depolarization-induced inhibition of glial transporter activity, because it was occluded by TBOA and DHK. In agreement, pH 7.0 did not directly alter D-aspartate-induced responses in NTS glia or properties of presynaptic glutamate release. Thus acidification-dependent regulation of glial function affects synaptic transmission within the NTS. These results suggest that glia play a modulatory role in the NTS by integrating local tissue signals (such as pH) with synaptic inputs from peripheral afferents. [ABSTRACT FROM AUTHOR]