PHORBOL ESTER EFFECT AT HIPPOCAMPAL SYNAPSES ACT INDEPENDENTLY OF THEGAMMA-ISOFORM OF PMC

Ca2+/phospholipid-dependent protein kinase has long been thought to pl ay an important role in modulating synaptic efficacy. It has been show n previously that mice lacking the brain-specific gamma subtype of PKC display abnormal long-term potentiation (LTP), whereas ordinary synap tic transmission is unaffected. by the mutation. We now examine the ef fects of phorbol esters, which are nonselective activators of PKC, on synaptic modulation in these mutant mice. In wild-type mice, phorbol e sters produce marked enhancement of synaptic transmission that is larg ely presynaptic in origin, an effect that has been thought to share me chanisms with LTP. In mutant mice, phorbol ester-mediated potentiation is normal despite the absence of the major PRC isoform. As in wild-ty pe mice, this synaptic enhancement is at lease partly attributable to presynaptic changes. Our results demonstrate that the gamma isotype of PKC is not essential for phorbol ester-mediated synaptic facilitation , and place limitations on the possible roles of PKC in LTP.