Increased density and stabilization of climbing fiber-Purkinje cell synapses in mice overexpressing corticotropin-releasing factor

Corticotropin-releasing factor (CRF) plays a crucial role in generating the stress response. During early development CRF also acts as a neuromodulator and triggers neurite outgrowth. Here, we evaluate the effects of CRF on afferent systems of cerebellar Purkinje cells using mice overexpressing CRF, particularly in brain. We hypothesize that CRF not only stimulates dendritic development, but additionally is involved in the process of axon-target development and synapse formation more specifically of climbing fiber afferent input. We demonstrate that over expression of CRF does not affect Purkinje cells in cerebellum, but leads to marked changes in the pattern of distribution of climbing fibers. However, the parallel fiber system, that does not express CRF, is not affected by the overabundance of CRF. Thus, CRF might be strategically distributed and hence involved in the regulation of the formation and stabilization of synapses between climbing fibers and Purkinje cells, selectively with respect to the proximal and middle parts of the dendritic trees of Purkinje cells, and is not involved in the parallel fiber input on the Purkinje cell.