This study of rat cerebellar slices yielded two lines of evidence indicatin
g that the corticotropin-releasing factor (CRF) found in climbing fibers (C
Fs) is critical for the induction of long-term depression (LTD) at the para
llel fiber (PF) synapses of Purkinje cells (PCs) by their conjunctive activ
ation with either stimulation of CFs or depolarization of PCs, First, LTD i
nduction was effectively blocked by specific CRF receptor antagonists, alph
a-helical CRF-(9-41) (alpha-h CRF) and astressin; and second, LTD was no lo
nger observed in CF-deprived cerebella but was restored by CRF replenishmen
t, The data obtained in this study suggest that these effects are mediated
by protein kinase C (PKC) and not by Ca2+ signaling or cyclic GMP (cGMP) pr
oduction.