Inactivation of Serotonergic Neurons in the Rostral Medullary Raphé Attenuates Stress-Induced Tachypnea and Tachycardia in Mice

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Ikoma, Yoko
Kusumoto-Yoshida, Ikue
Yamanaka, Akihiro
Ootsuka, Youichirou
Kuwaki, Tomoyuki
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Frontiers Media
The medullary raphé nuclei are involved in controlling cardiovascular, respiratory, and thermoregulatory functions, as well as mediating stress-induced tachycardia and hyperthermia. Although the serotonergic system of the medullary raphé has been suggested as the responsible entity, specific evidence has been insufficient. In the present study, we tested this possibility by utilizing an optogenetic approach. We used genetically modified mice [tryptophan hydroxylase 2 (Tph2); archaerhodopsin-T (ArchT) mice] in which ArchT, a green light-driven neuronal silencer, was selectively expressed in serotonergic neurons under the regulation of Tph2 promoters. We first confirmed that an intruder stress selectively activated medullary, but not dorsal or median raphé serotonergic neurons. This activation was suppressed by photo-illumination via a pre-implanted optical fiber, as evidenced by the decrease of a cellular activation marker protein in the neurons. Next, we measured electro cardiogram (ECG), respiration, body temperature (BT), and locomotor activity in freely moving mice during intruder and cage-drop stress tests, with and without photo-illumination. In the intruder test, photo inactivation of the medullary serotonergic neurons significantly attenuated tachycardia (362 ± 58 vs. 564 ± 65 bpm.min, n = 19, p = 0.002) and tachypnea (94 ± 82 vs. 361 ± 138 cpm.min, n = 9, p = 0.026), but not hyperthermia (1.0 ± 0.1 vs. 1.0 ± 0.1∘C.min, n = 19, p = 0.926) or hyperlocomotion (17 ± 4 vs. 22 ± 4, arbitrary, n = 19, p = 0.089). Similar results were obtained from cage-drop stress testing. Finally, photo-illumination did not affect the basal parameters of the resting condition. We conclude that a subpopulation of serotonergic neurons in the medullary raphé specifically mediate stress-induced tachypnea and tachycardia, which have little involvement in the basal determination of respiratory frequency (Res) and heart rate (HR), specifically mediate stress-induced tachycardia and tachypnea.
Note: This article was submitted to Integrative Physiology, a section of the journal Frontiers in Physiology. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
serotonin, medullary raphe, stress, respiration, circulation, body temperature
Ikoma, Y., Kusumoto-Yoshida, I., Yamanaka, A., Ootsuka, Y. and Kuwaki, T., (2018). Inactivation of Serotonergic Neurons in the Rostral Medullary Raphé Attenuates Stress-Induced Tachypnea and Tachycardia in Mice. Front. Physiol. 9:832. doi: 10.3389/fphys.2018.00832.