CRF and urocortin differentially modulate GluRδ2 expression and distribution in parallel fiber-Purkinje cell synapses

Corticotropin-releasing factor (CRF) and urocortin (UCN) are closely related multifunctional regulators, governing, among other processes, Purkinje cell development. Here, we investigate the effects of CRF and UCN on Purkinje cells in organotypic slices. We show that both peptides upregulate δ2 ionotropic glutamate receptor gene expression, and increase the abundance of the receptor in the postsynaptic density. However, only UCN treatment results in increased δ2 protein level per Purkinje cell, implying the existence of posttranscriptional regulation of GluRδ2 mRNA. CRF, in contrast, reduces the number of δ2-positive dendritic shafts per cell, implying that the increase of GluRδ2 in remaining synapses may be mainly due to its retargeting. We further observed different patterns of GluRδ2 distribution in the zone of postsynaptic density upon CRF and UCN treatment. CRF treatment results in a clustered distribution of GluRδ2 along the postsynaptic density, whereas UCN treatment provides a linear distribution.