Cerebellar Control of Defense Reactions under Orexin-mediated Neuromodulation as a Model of Cerebellohypothalamic Interaction

Recent evidence has indicated that, when an animal is exposed to harmful stimuli, hypothalamic orexinergic neurons are activated via the amygdala and in turn tune the neuronal circuits in the spinal cord, brainstem, and an area of the cerebellum (folium-p of the flocculus) by neuromodulation. The animal would then initiate “defense reactions” composed of complex movements and associated cardiovascular responses. To investigate neuronal mechanisms of the defense reactions, Nisimaru et al. (2013) analyzed cardiovascular responses induced by an electric foot shock stimulus to a rabbit and found two major effects. One is redistribution of arterial blood flow from visceral organs to active muscles, and the other is a modest increase in blood pressure. Kainate-induced lesions of folium-p impaired these two effects. Moreover, folium-p Purkinje cells were shown to project to the parabrachial nucleus, one of the major cardiovascular centers in the brainstem. These data indicate that folium-p Purkinje cells regulate cardiovascular defense reactions via parabrachial nucleus under orexin-mediated neuromodulation. In this article, we review these data from the viewpoint that the defense reactions are expressions of “anger and anxiety”, which respectively lead to “fight and flight” behaviors. The present orexin case may provide a model of cerebellohypothalamic interactions via neuropeptides or amines of hypothalamic origin, which may underlie various types of emotion and behavior.