{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T18:10:27Z","timestamp":1777313427840,"version":"3.51.4"},"reference-count":88,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T00:00:00Z","timestamp":1746403200000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:sec><jats:title>Abstract<\/jats:title><jats:p>Viscerosensory afferent neurons of the vagus nerve form excitatory synapses onto second\u2010order neurons in the brainstem nucleus of the solitary tract (NTS). Vagal afferent neurons release glutamate via functionally distinct action potential\u2010dependent (evoked) and \u2010independent (spontaneous) release pathways. Current models remain conflicted regarding whether synapses maintain physically and functionally separate vesicle pools underlying each release pathway or if they are unified via a common pool of vesicles. Most evidence has been derived from neurons in the CNS, so it remains unclear whether there are shared or distinct vesicle pools for both forms of release within terminals of peripheral sensory neurons. Here we aimed to determine the functional organization of vesicles used for evoked <jats:italic>versus<\/jats:italic> spontaneous glutamate release from vagal afferent terminals. We performed whole\u2010cell patch\u2010clamp electrophysiology on NTS neurons within acute rat brainstem slices and measured glutamatergic EPSCs combined with pharmacological use\u2010dependent inhibition of presynaptic vesicle filling or postsynaptic NMDA receptor blockade. Despite the differences in functional characteristics between evoked and spontaneous release, we found that a common population of presynaptic vagal afferent vesicles and postsynaptic glutamate receptors were used for both action potential\u2010evoked and activity\u2010independent spontaneous transmission pathways. We conclude that at vagal afferent terminals, vesicle release pathways pull from a common vesicle pool while exhibiting functionally distinct controls and points of regulation. This vesicle handling strategy may allow for shared resources while preserving distinct information types encoded by spontaneous and evoked release that are important for transmission of viscerosensory information.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp16726-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Evoked and spontaneous glutamate release from vagal afferent neurons onto the nucleus of the solitary tract (NTS) appear to be functionally different processes with distinct mechanisms controlling their release.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Preventing spontaneously released vesicles from refilling with glutamate reveals that spontaneous and evoked release draw from a common pool of synaptic vesicles in vagal afferent terminals.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Evoked and spontaneously released glutamate targets a shared population of postsynaptic NMDA receptors.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Spontaneous glutamate release controls baseline NTS action potential firing but does not impact solitary tract\u2010evoked action potential throughput.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1113\/jp288301","type":"journal-article","created":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T07:26:31Z","timestamp":1746429991000},"page":"3141-3159","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Functionally distinct evoked and spontaneous neurotransmission operate via a shared pool of synaptic vesicles in viscerosensory afferents"],"prefix":"10.1113","volume":"603","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8744-5946","authenticated-orcid":false,"given":"Rachel A.","family":"Arnold","sequence":"first","affiliation":[{"name":"Department of Integrative Physiology and Neuroscience, College of Veterinary Medicine Washington State University  Pullman WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6501-2502","authenticated-orcid":false,"given":"James H.","family":"Peters","sequence":"additional","affiliation":[{"name":"Department of Integrative Physiology and Neuroscience, College of Veterinary Medicine Washington State University  Pullman WA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,5,5]]},"reference":[{"issue":"4","key":"e_1_2_5_2_1","first-page":"H1307","article-title":"Non\u2010NMDA receptors mediate sensory afferent synaptic transmission in medial nucleus tractus solitarius","volume":"259","author":"Andresen M. 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