SDF-1 alpha-mediated modulation of synaptic transmission in rat cerebellum

The functional expression of the seven-transmembrane domain G protein-coupl ed chemokine receptor CXCR-4/fusin in rat nerve cell was demonstrated by st aining with a polyclonal anti-CXCR-4 Ab, and by evaluating the calcium resp onses to the physiological agonist stromal-derived cell factor-1 alpha (SDF -1 alpha) in both cerebellar granule cells in culture and Purkinje neurons (PNs) in cerebellar slices. Cerebellar glial, granule and Purkinje cells sh owed a pronounced staining for CXCR-4. Furthermore, cultured granule cells exhibited Ca2+ transients elicited by the application of SDF-1 alpha, both in cell bodies and in neuronal processes. Whole-cell patch-clamped PNs in c erebellar slices responded to SDF-1 alpha application by a slow inward curr ent followed by an increase of both intracellular Ca2+ level and spontaneou s synaptic activity. In particular, the SDF-1 alpha-induced slow inward cur rent was considerably reduced by ionotropic glutamate receptor blockers, bu t developed fully in a medium in which synaptic transmission was inhibited, indicating that this current might be, at least in part, mediated by extra synaptic glutamate, possibly released from the surrounding glial and/or ner ve cells. Taken together, these findings indicate a functional involvement of CXCR-4 in the modulation of synaptic transmission, adding another member to the repertoire of the chemokine receptors exerting a neuromodulatory ro le in the cerebellum.