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Previous studies suggest that this collapse of autonomic control may be caused by thrombin acting on astrocytic protease-activated receptors (PAR1) in the hindbrain. Using calcium imaging and electrophysiological techniques, we evaluated the mechanisms by which astrocytic PAR1s modulate the activity of presynaptic vagal afferent terminals and postsynaptic neurons in the rat nucleus of the solitary tract (NST). Our calcium-imaging data show that astrocytic and neuronal calcium levels increase after brain slices are treated with the PAR1 agonist SFLLRN-NH<jats:sub>2<\/jats:sub>. This increase in activity is blocked by pretreating the slices with the glial metabolic blocker fluorocitrate. In addition, PAR1-activated astrocytes communicate directly with NST neurons by releasing glutamate. Calcium responses to SFLLRN-NH<jats:sub>2<\/jats:sub>in the astrocytes and neurons significantly increase after bath application of the excitatory amino acid transporter blocker<jats:sc>dl<\/jats:sc>-threo-\u03b2-benzyloxyaspartic acid (TBOA) and significantly decrease after bath application of the NMDA receptor antagonist<jats:sc>dl<\/jats:sc>-2-amino-5-phosphonopentanoic acid (<jats:sc>dl<\/jats:sc>-AP5). Furthermore, astrocytic glutamate activates neuronal GluN2B-containing NMDA receptors. Voltage-clamp recordings of miniature EPSCs (mEPSCs) from NST neurons show that astrocytes control presynaptic vagal afferent excitability directly under resting and activated conditions. Fluorocitrate significantly decreases mEPSC frequency and SFLLRN-NH<jats:sub>2<\/jats:sub>significantly increases mEPSC frequency. These data show that astrocytes act within a tripartite synapse in the NST, controlling the excitability of both postsynaptic NST neurons and presynaptic vagal afferent terminals.<\/jats:p>","DOI":"10.1523\/jneurosci.3105-14.2015","type":"journal-article","created":{"date-parts":[[2015,1,14]],"date-time":"2015-01-14T17:43:24Z","timestamp":1421257404000},"page":"776-785","source":"Crossref","is-referenced-by-count":52,"title":["PAR1-Activated Astrocytes in the Nucleus of the Solitary Tract Stimulate Adjacent Neurons via NMDA Receptors"],"prefix":"10.1523","volume":"35","author":[{"given":"Katie M.","family":"Vance","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard C.","family":"Rogers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0405-2820","authenticated-orcid":false,"given":"Gerlinda 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