BLOCK OF INDUCTION AND MAINTENANCE OF CALCIUM-INDUCED LTP BY INHIBITION OF PROTEIN-KINASE-C IN POSTSYNAPTIC NEURON IN HIPPOCAMPAL CA1 REGION

Calcium-induced LTP (Ca-LTP) refers to the long-lasting potentiation of synaptic transmission in hippocampal synapses that can be induced by a transient (7-10 min) and small increase (from 2 mM to 4 mM) in extracellular calcium concentration. In this paper the effects of protein kinase C (PKC) inhibitors, polymyxin B (PMB) and PKC(19-31), given intracellularly to the postsynaptic neuron in the CA1 region, on the induction and maintenance of Ca-LTP were studied and compared with those found in a similar study earlier made in this laboratory on tetanic stimulation-induced LTP (TS-LTP) [18]. When the intracellular delivery of the inhibitor(s) was made to begin 30 min before the exposure to increased [Ca2+](0), the development of Ca-LTP was completely blocked, leaving only a brief enhancement of EPSPs directly attributable to the brief increase in [Ca2+](0). When the intracellular delivery of either PKC(19-31) alone or PMB + PKC(19-31) was made to begin after the full establishment of Ca-LTP, it soon made the maintained potentiation begin to decline, the EPSP amplitude gradually returning to the control value before the exposure to increased calcium. Thus postsynaptic PKC inhibition blocks both the induction and the maintenance of Ca-LTP, just as it has been shown to do to TS-LTP. But quantitative differences exist: both the induction and the maintenance of Ca-LTP appeared to be more susceptible to block by postsynaptic PKC inhibition than those of TS-LTP.