Calcitonin gene-related peptide modulates neuronal activity in the mammalian cerebellar cortex

Calcitonin gene related peptide (CGRP) has been localized within specific populations of mossy fibers in the cat's cerebellar cortex. The intent of the present study was to determine the physiological role of this peptide in cerebellar circuitry. CGRP was iontophoretically applied and its effects on spontaneous, amino acid-induced, and synaptically-mediated activity were recorded. In addition, interactions between CGRP and serotonin (5HT), another neuromodulator in cerebellar circuitry, also were analyzed. The findings of this study reveal that the primary effect of CGRP is to suppress spontaneous and excitatory amino acid-induced activity. However, CGRP has a more potent effect in suppressing aspartate- and quisqualate-induce activity as compared to that elicited by glutamate. CGRP slowed or completely blocked synaptic activity mediated by stimulation of the inferior cerebellar peduncle. Finally, the individual suppressive effects of 5HT and CGRP were potentiated when both were applied simultaneously. However, the potentiation was greater when the neuron was exposed to 5HT before CGRP was applied. In summary, the presence of CGRP in selected populations of mossy fibers, together with serotoninergic afferents, decreases the responsiveness of Purkinje cells to excitatory amino acids as well as synaptically-driven activity. Thus, activation of an afferent system to the cerebellum can elicit distinct effects on different populations of neurons that are dependent on the microenvironment of the cell at a particular point in time.