VGLUT2-expressing neurons in the vestibular nuclear complex mediate gravitational stress-induced hypothermia in mice.

The vestibular system, which is essential for maintaining balance, contributes to the sympathetic response. Although this response is involved in hypergravity load-induced hypothermia in mice, the underlying mechanism remains unknown. This study showed that hypergravity (2g) decreased plasma catecholamines, which resulted in hypoactivity of the interscapular brown adipose tissue (iBAT). Hypothermia induced by 2g load was significantly suppressed by administration of beta-adrenergic receptor agonists, suggesting the involvement of decrease in iBAT activity through sympathoinhibition. Bilateral chemogenetic activation of vesicular glutamate transporter 2 (VGLUT2)-expressing neurons in the vestibular nuclear complex (VNC) induced hypothermia. The VGLUT2-expressing neurons contributed to 2g load-induced hypothermia, since their deletion suppressed hypothermia. Although activation of vesicular gamma-aminobutyric acid transporter-expressing neurons in the VNC induced slight hypothermia instead of hyperthermia, their deletion did not affect 2g load-induced hypothermia. Thus, we concluded that 2g load-induced hypothermia resulted from sympathoinhibition via the activation of VGLUT2-expressing neurons in the VNC.

Hypergravity-induced plastic alteration of the vestibulo-sympathetic reflex involves decrease in responsiveness of CAMK2-expressing neurons in the vestibular nuclear complex.

The vestibular system contributes to not only eye movement and posture but also the sympathetic response. Plastic alteration of the vestibulo-sympathetic reflex is induced by hypergravity load; however, the mechanism remains unknown. Here, we examined 2 g-induced changing in responsiveness of CAMK2-expressing neurons in the vestibular nucleus complex using optogenetic tools. The excitatory photostimulation of the CAMK2-expressing neurons in the unilateral vestibular nuclear complex induced body tilt to the contralateral side, while inhibitory photostimulation showed the opposite response. Photoactivation of either cell body or the axonal terminal in the rostral ventrolateral medulla showed sympathoexcitation followed by the pressor response. Furthermore, this response was significantly attenuated (49.8 ± 4%) after the 1st day of 2 g loading, and this value was further reduced by the 5th day (22.4 ± 3%), suggesting that 2 g-induced attenuation of the vestibulo-sympathetic reflex involves at least decrease in responsiveness of CAMK2-expressing neurons in the vestibular nuclear complex.