Orexin-neuromodulated cerebellar circuit controls redistribution of arterial blood flows for defense behavior in rabbits.

Naoko Nisimaru, Chetan Mittal, Yoshinori Shirai, Thongchai Sooksawate, Prabu Anandaraj, Tsutomu Hashikawa, Soichi Nagao, Akiko Arata, Takeshi Sakurai, Miyuki Yamamoto, Masao Ito

Proceedings of the National Academy of Sciences of the United States of America 2013 Aug 27

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We investigated a unique microzone of the cerebellum located in folium-p (fp) of rabbit flocculus. In fp, Purkinje cells were potently excited by stimulation of the hypothalamus or mesencephalic periaqueductal gray, which induced defense reactions. Using multiple neuroscience techniques, we determined that this excitation was mediated via beaded axons of orexinergic hypothalamic neurons passing collaterals through the mesencephalic periaqueductal gray. Axonal tracing studies using DiI and biotinylated dextran amine evidenced the projection of fp Purkinje cells to the ventrolateral corner of the ipsilateral parabrachial nucleus (PBN). Because, in defense reactions, arterial blood flow has been known to redistribute from visceral organs to active muscles, we hypothesized that, via PBN, fp adaptively controls arterial blood flow redistribution under orexin-mediated neuromodulation that could occur in defense behavior. This hypothesis was supported by our finding that climbing fiber signals to fp Purkinje cells were elicited by stimulation of the aortic nerve, a high arterial blood pressure, or a high potassium concentration in muscles, all implying errors in the control of arterial blood flow. We further examined the arterial blood flow redistribution elicited by electric foot shock stimuli in awake, behaving rabbits. We found that systemic administration of an orexin antagonist attenuated the redistribution and that lesioning of fp caused an imbalance in the redistribution between active muscles and visceral organs. Lesioning of fp also diminished foot shock-induced increases in the mean arterial blood pressure. These results collectively support the hypothesis that the fp microcomplex adaptively controls defense reactions under orexin-mediated neuromodulation.

Citation

Naoko Nisimaru, Chetan Mittal, Yoshinori Shirai, Thongchai Sooksawate, Prabu Anandaraj, Tsutomu Hashikawa, Soichi Nagao, Akiko Arata, Takeshi Sakurai, Miyuki Yamamoto, Masao Ito. Orexin-neuromodulated cerebellar circuit controls redistribution of arterial blood flows for defense behavior in rabbits. Proceedings of the National Academy of Sciences of the United States of America. 2013 Aug 27;110(35):14124-31