B-50 GAP-43 PHOSPHORYLATION AND PKC ACTIVITY ARE INCREASED IN RAT HIPPOCAMPAL SYNAPTOSOMAL MEMBRANES AFTER AN INHIBITORY AVOIDANCE TRAINING/

Several lines of evidence indicate that protein kinase C (PKC) is invo lved in long-term potentiation (LTP) and in certain forms of learning. Recently, we found a learning-specific, time-dependent increase in [H -3]phorbol dibutyrate binding to membrane-associated PKC in the hippoc ampus of rats subjected to an inhibitory avoidance task. Here we confi rm and extend this observation, describing that a one trial inhibitory avoidance learning was associated with rapid and specific increases i n B-50/GAP-43 phosphorylation in vitro and in PKC activity in hippocam pal synaptosomal membranes. The increased phosphorylation of B-50/GAP- 43 was seen at 30 min (+35% relative to naive or shocked control group s), but not at 10 or 60 min after training. This learning-associated i ncrease in the phosphorylation of B-50/GAP-43 is mainly due to an incr ease in the activity of PKC. This is based on three different sets of data: 1) PKC activity increased by 24% in hippocampal synaptosomal mem branes of rats sacrificed 30 min after training; 2) B-50/GAP-43 immuno blots revealed no changes in the amount of this protein among the diff erent experimental groups; 3) phosphorylation assays, performed in the presence of bovine purified PKC or in the presence of the selective P KC inhibitor CGP 41231, exhibited no differences in B-50/GAP-43 phosph orylation between naive and trained animals. In conclusion, these resu lts support the contention that hippocampal PKC participates in the ea rly neural events of memory formation of an aversively-motivated learn ing task.