Optogenetic inhibition of Purkinje cell activity reveals cerebellar control of blood pressure during postural alterations in anesthetized rats.

The cerebellar uvula (lobule IX), a part of the vestibulocerebellum, is extensively connected to the areas of the brainstem that participate in cardiovascular regulation and vestibular signal processing. This suggests that the uvula regulates blood pressure (BP) during postural alterations. Previous studies showed that lesions of the uvula affected the baroreceptor reflex and cardiovascular responses during postural alterations. To investigate the mechanisms underlying this BP regulation, it is necessary to have a method to selectively modulate the activity of Purkinje cells (PCs), the sole output neurons from the cerebellar cortex, without affecting other neuronal types such as local interneurons or nonlocal neurons that send their axons to the cerebellar cortex. We recently developed a novel technique using optogenetics to manipulate PC activity and showed that activation and inhibition of PCs in the uvula either decreased or increased the resting BP, respectively. This technique was employed in the current study to examine the roles of the uvula in BP regulation during postural alterations in anesthetized rats. Enhanced Natronomonas pharaonis halorhodopsin (eNpHR), a light-driven chloride ion pump, was selectively expressed in uvular PCs using a lentiviral vector containing the PC-specific L7 promoter. The eNpHR-expressing PCs were then illuminated by orange laser (593 nm) either during 30° head-up or 30° head-down tilts. The eNpHR-mediated photoinhibition of the uvula attenuated the extent of BP recovery after a BP increase induced by postural changes during head-down tilts. By contrast, photoinhibition had no statistically significant effect on BP recovery during head-up tilts. The effects of photoinhibition on BP during tilts were significantly different from those observed during the resting condition, indicating that cerebellar control of BP during tilts is dynamic rather than static. Taken together, these results suggest that PCs in the uvula dynamically regulates BP maintenance during postural alterations.