Evidence for the presence of the type 2 corticotropin releasing factor receptor in the rodent cerebellum

Abstract

Corticotropin releasing factor (CRF), localized in afferent inputs to the cerebellum, binds to two receptors defined as the Type 1 (CRF-R1) and the Type 2 (CRF-R2alpha). CRF-R1 has been localized to the cerebellum, as has a truncated isoform of CRF-R2alpha. Evidence for the presence of the full length isoform of CRF-R2alpha in the cerebellum is conflicting. We used RT-PCR, immunohistochemical, and physiologic techniques to resolve this conflict. RT-PCR data show low levels of CRF-R2alpha in the vermis and hemisphere of the cerebellum. These observations were confirmed by the Gene Expression Nervous System Atlas (GENSAT) database. A CRF-R2alpha antibody was used to determine the cellular distribution of the receptor in the cerebellum. The vast majority of the receptors are localized to Bergmann glial cells located throughout the cerebellum, as well as astrocytes in the granule cell layer. Neuronal labeling is present in sub-populations of Purkinje cells, Golgi cells, basket cells, and cerebellar nuclear neurons. Physiologic data show that urocortin II, which binds selectively to CRF-R2alpha, increases the firing rate of both Purkinje cells and nuclear neurons; this response can be blocked by the CRF-R2alpha-specific antagonist, antisauvagine-30. The present results confirm that CRF-R2alpha is present in the cerebellum and functions in circuits that modulate the firing rate of Purkinje cells and cerebellar nuclear neurons. A comparative analysis showed that the patterns of distribution of CRF-R1, CRF-R2alpha and CRF-R2alpha-tr are distinct. These data indicate that the CRF family of peptides modulates cerebellar output by binding to multiple CRF receptors.