{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T11:59:23Z","timestamp":1740139163782,"version":"3.37.3"},"reference-count":34,"publisher":"American Physiological Society","issue":"2","funder":[{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute (NHBLI)","doi-asserted-by":"publisher","award":["HL 112996","HL 007852"],"award-info":[{"award-number":["HL 112996","HL 007852"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs (VA)","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Applied Physiology"],"published-print":{"date-parts":[[2017,2,1]]},"abstract":"<jats:p> Unilateral dialysis of the broad-spectrum muscarinic receptor antagonist atropine (50 mM) into the ventral respiratory column [(VRC) including the pre-B\u00f6tzinger complex region] of awake goats increased pulmonary ventilation (V\u0307i) and breathing frequency (f), conceivably due to local compensatory increases in serotonin (5-HT) and substance P (SP) measured in effluent mock cerebral spinal fluid (mCSF). In contrast, unilateral dialysis of a triple cocktail of antagonists to muscarinic (atropine; 5 mM), neurokinin-1, and 5-HT receptors does not alter V\u0307i or f, but increases local SP. Herein, we tested hypotheses that 1) local compensatory 5-HT and SP responses to 50 mM atropine dialyzed into the VRC of goats will not differ between anesthetized and awake states; and 2) bilateral dialysis of the triple cocktail of antagonists into the VRC of awake goats will not alter V\u0307i or f, but will increase local excitatory neuromodulators. Through microtubules implanted into the VRC of goats, probes were inserted to dialyze mCSF alone (time control), 50 mM atropine, or the triple cocktail of antagonists. We found 1) equivalent increases in local 5-HT and SP with 50 mM atropine dialysis during wakefulness compared with isoflurane anesthesia, but V\u0307i and f only increased while awake; and 2) dialyses of the triple cocktail of antagonists increased V\u0307i, f, 5-HT, and SP (&lt;0.05) during both day and night studies. We conclude that the mechanisms governing local neuromodulator levels are state independent, and that bilateral excitatory receptor blockade elicits an increase in breathing, presumably due to a local, (over)compensatory neuromodulator response. <\/jats:p><jats:p> NEW &amp; NOTEWORTHY The two major findings are as follows: 1) during unilateral dialysis of 50 mM atropine into the ventral respiratory column to block excitatory muscarinic receptor activity, a compensatory increase in other neuromodulators was state independent, but the ventilatory response appears to be state dependent; and 2) the hypothesis that absence of decreased V\u0307i and f during unilateral dialysis of excitatory receptor antagonists was due to compensation by the contralateral VRC was not supported by findings herein. <\/jats:p>","DOI":"10.1152\/japplphysiol.00619.2016","type":"journal-article","created":{"date-parts":[[2016,9,29]],"date-time":"2016-09-29T22:58:35Z","timestamp":1475189915000},"page":"327-338","source":"Crossref","is-referenced-by-count":6,"title":["State-dependent and -independent effects of dialyzing excitatory neuromodulator receptor antagonists into the ventral respiratory column"],"prefix":"10.1152","volume":"122","author":[{"suffix":"III","given":"Thomas M.","family":"Langer","sequence":"first","affiliation":[{"name":"Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzanne E.","family":"Neumueller","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma","family":"Crumley","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas J.","family":"Burgraff","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sawan","family":"Talwar","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew R.","family":"Hodges","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin;"},{"name":"Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin; 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