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Rostral cuneiform nucleus and the defense reaction: Direct and indirect midbrain-medullary serotonin mechanisms in baroreflex inhibition
  • Florence Netzer,
  • Caroline Sévoz-Couche
Florence Netzer
UMR_S 1158

Corresponding Author:[email protected]

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Caroline Sévoz-Couche
UMR_S 1158
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Background and Purpose: The activation of the defense reaction inhibits the baroreflex response through the B3 and nucleus tractus solitarius (NTS) regions. Our aim was to determine whether and how baroreflex inhibition induced by the disinhibition of the rostral cuneiform nucleus, part of the defense pathway, involves serotonin cells in B3 and 5-HT3 receptors in the NTS. Experimental Approach: We performed immunohistochemistry and anatomical experiments to determine whether raphe serotonin cells expressing Fos were directly targeted by the rostral cuneiform nucleus. The effect of blocking raphe serotonin transmission and NTS 5-HT3 receptors, on cuneiform-induced inhibition of the baroreflex cardiac response, were also analyzed. Key Results: Bicuculline microinjected into the rostral cuneiform nucleus induced an increase of double labeled Fos-5-HT IR cells in both the LPGi and Raphe Magnus. The anterograde tracer Phaseolus vulgaris leucoaggutinin into the rostral cuneiform nucleus revealed a dense projection to the LPGi but not Raphe Magnus. Cuneiform-induced baroreflex inhibition was prevented by B3 injection of 8-OH-DPAT, a specific agonist for 5-HT1A receptors. Cuneiform disinhibition also failed to inhibit the baroreflex bradycardia after microinjection of a 5-HT3 receptor antagonist (granisetron) into the NTS or in 5-HT3 receptor knock-out mice. Conclusion and Implications: In conclusion, the rostral cuneiform nucleus participates in the defense inhibition of the baroreflex bradycardia via direct activation of the LPGi and a relay to the Raphe Magnus, to activate NTS 5-HT3 receptors and inhibit second-order baroreflex neurons. These data bring new insights in primary and secondary mechanisms involved in vital baroreflex prevention during stress.
05 Oct 2020Submitted to British Journal of Pharmacology
06 Oct 2020Submission Checks Completed
06 Oct 2020Assigned to Editor
19 Oct 2020Reviewer(s) Assigned
15 Nov 2020Review(s) Completed, Editorial Evaluation Pending
03 Dec 2020Editorial Decision: Revise Minor
17 Dec 20201st Revision Received
20 Dec 2020Submission Checks Completed
20 Dec 2020Assigned to Editor
04 Jan 2021Reviewer(s) Assigned
20 Jan 2021Review(s) Completed, Editorial Evaluation Pending
23 Jan 2021Editorial Decision: Accept