Neuromodulatory effects of corticotropin releasing factor on cerebellar Purkinje cells: an in vivo study in the cat.

Corticotropin releasing factor, a 41 amino acid peptide, has been localized in climbing fibers and mossy fibers in the cat's cerebellar cortex. In the present study, corticotropin releasing factor was iontophoretically applied to Purkinje cells, isolated extracellularly, to assess the effect of this peptide on the firing rate of the neuron. By itself corticotropin releasing factor had little or no effect on cellular activity. However, this peptide potentiated the excitatory effects of aspartate and glutamate, the putative neurotransmitters of the climbing fiber and mossy fiber-parallel fiber systems, respectively. In addition, corticotropin releasing factor blocked the suppressive effects induced by the iontophoretic application of GABA. Finally, it shortened or eliminated the period of suppression produced by activation of climbing fibers in the cerebellar cortex. These data suggest that corticotropin releasing factor functions as a neuromodulator rather than as a neurotransmitter in cerebellar circuitry.