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Our aim was to determine whether and how baroreflex inhibition, induced by the disinhibition of the rostral cuneiform nucleus (part of the defence pathway), involves 5\u2010HT neurons in B3 and 5\u2010HT<jats:sub>3<\/jats:sub> receptors in the NTS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>We performed immunohistochemistry and anatomical experiments to determine whether raph\u00e9 5\u2010HT cells expressing Fos were directly targeted by the rostral cuneiform nucleus. The effect of blocking raph\u00e9 5\u2010HT neurotransmission and NTS 5\u2010HT<jats:sub>3<\/jats:sub> receptors on cuneiform\u2010induced inhibition of the baroreflex cardiac response were also analysed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Bicuculline, microinjected into the rostral cuneiform nucleus, induced an increase of double\u2010labelled Fos\u20105\u2010HT\u2010IR cells in both the lateral paragigantocellular nucleus (LPGi) and raph\u00e9 magnus. The anterograde tracer <jats:italic>Phaseolus vulgaris<\/jats:italic> leucoaggutinin injected into the rostral cuneiform nucleus revealed a dense projection to the LPGi but not raph\u00e9 magnus. Cuneiform\u2010induced baroreflex inhibition was prevented by B3 injection of 8\u2010OH\u2010DPAT, a selective 5\u2010HT<jats:sub>1A<\/jats:sub> receptor agonist. Cuneiform disinhibition also failed to inhibit the baroreflex bradycardia after NTS microinjection of the 5\u2010HT<jats:sub>3<\/jats:sub> receptor antagonist granisetron and in 5\u2010HT<jats:sub>3<\/jats:sub> receptor knockout mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>The rostral cuneiform nucleus participates in the defence inhibition of the baroreflex bradycardia via direct activation of the LPGi and via a projection to the raph\u00e9 magnus to activate NTS 5\u2010HT<jats:sub>3<\/jats:sub> receptors and inhibit second\u2010order baroreflex neurons. These data bring new insights in primary and secondary mechanisms involved in vital baroreflex prevention during stress.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15406","type":"journal-article","created":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T18:11:47Z","timestamp":1612548707000},"page":"1819-1835","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Rostral cuneiform nucleus and the defence reaction: Direct and indirect midbrain\u2013medullary 5\u2010HT mechanisms in baroreflex inhibition"],"prefix":"10.1111","volume":"178","author":[{"given":"Florence","family":"Netzer","sequence":"first","affiliation":[{"name":"INSERM U894, Centre of Psychiatry and Neurosciences  Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"S\u00e9voz\u2010Couche","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, INSERM, UMRS1158, Neurophysiologie 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