Modulatory role of neuropeptides in the cerebellum

Abstract

The existence of neuropeptides in the central nervous system has been known for almost 40 years. Within the cerebellum approximately 22 neuropeptides have been identified. However, the functional role(s) for many of the different peptides in the cerebellum is largely unknown as their distribution in the cerebellum is not uniform and varies between species. Further, to date sufficient physiological analysis has not been carried out to determine the potential importance of cerebellar peptides. It has been proposed that peptides slowly modulate cerebellar circuits by acting through G protein-coupled receptors in contrast to the fast action of amino acid neurotransmitters that bind to ionotropic receptors. This effect, in turn, would influence the state of an entire neuronal circuit rather than a single neuron. This chapter will be focused on two members of the corticotropin-releasing factor (CRF) family of peptides, namely, corticotropin-releasing factor and urocortin because their distribution has been described in multiple species and their function has been investigated to a greater extent than any of the other peptides found in the cerebellum. A review of the distribution of these peptides as well as a discussion of their cognate receptors is included. Data on the functional role of both peptides is presented. It is clear that complex interactions take place between these peptides and other transmitters in the cerebellum. The physiological data suggest that CRF is essential for normal cerebellar-mediated motor performance. There is less data on the physiological role of urocortin (UCN) in the cerebellum. To date, it has been shown that UCN increases the spontaneous firing rate of Purkinje cells. The mechanisms by which this occurs are yet to be determined. Considering there are many other peptides in the cerebellum, it becomes clear that modulation by these peptides must be seriously considered when analyzing and interpreting physiological data related to cerebellar circuitry. The classic view that only glutamatergic or GABAergic inputs are relevant when describing the effects on firing rate, patterns of activation, output of the cortex or nuclei are no longer valid. Peptides are an integral component of cerebellar function and must be considered to completely understand cerebellar function.