Functional roles of neuropeptides in cerebellar circuits

Whereas the cerebellum contains 22 different types of neuropeptides as presently known, their expression is generally weak and diffusely dispersed in cerebellar tissues, which often makes their functional significance doubtful. Nevertheless, our knowledge about certain neuropeptides has advanced to the extent that we can figure out their unique functional roles in cerebellar circuits. Throughout the cerebellum, CRF is contained in climbing fibers and its spontaneous release is required for the induction of cerebellar long-term depression (LTD), a cellular mechanism of motor learning. Corticotropin-releasing factor (CRF) is also expressed in the paraventricular nucleus-pituitary system and amygdala-lower brainstem system, both of which are involved in coping responses to stress. In view that motor learning requires stressful efforts for correcting errors in repeated trials, CRF in climbing fibers may imply that the olivocerebellar system is part of a large CRF-operated functional system that acts to cope with various stressors. Orexin, on the other hand, is contained in beaded fibers, which, originating from the hypothalamus, project to various brainstem nuclei and also to the cerebellum, exclusively the flocculus. Currently available evidence suggests that, in fight-or-flight situations, orexinergic neurons switch the state of cardiovascular control systems including the flocculus to secure blood supply to working muscles. Considerable knowledge has also been accumulated about angiotensin II, galanin, and cerebellin, but there is still a gap in defining their unique functional roles in cerebellar circuits.