INTERACTION BETWEEN PAIRED-PULSE FACILITATION AND LONG-TERM POTENTIATION OF MINIMAL EXCITATORY POSTSYNAPTIC POTENTIALS IN RAT HIPPOCAMPAL SLICES - A PATCH-CLAMP STUDY

Long-term potentiation is an experimental paradigm used to study synap tic plasticity and memory mechanisms. One similarity between long-term potentiation and memory is the existence of several distinct phases. However, our preliminary quantal analysis did not reveal essential dif ferences in expression mechanisms of the early (<1 h) and later (up to 3 h) phases of long-term potentiation. The data were compatible with presynaptic mechanisms of both phases. Another approach to distinguish between presynaptic and postsynaptic mechanisms is analysis of intera ction between long-term potentiation and presynaptic paired-pulse faci litation. Such analysis had been previously done mainly with recording s of field potentials reflecting the activity of large neuronal popula tions. Only the early potentiation phase had been previously analysed with recordings from single neurons. The results from different groups were contradictory. In the present study, minimal excitatory postsyna ptic potentials were recorded from CA1 pyramidal neurons of rat hippoc ampal slices. Paired-pulse facilitation ratios were calculated for var ious periods (up to 2-3 h) following induction of long-term potentiati on. The ratio persistently decreased in the majority of neurons follow ing long-term potentiation induction. The decrease in the paired-pulse facilitation ratio correlated with the magnitude of long-term potenti ation and with the initial (pretetanic) facilitation ratio. Therefore, the general results of the present analysis was similar with the resu lts of the quantal analysis: it is consistent with a strong involvemen t of presynaptic mechanisms in maintenance of both early and late phas es of long-term potentiation. However, individual neurons could show v ariable changes in the paired-pulse facilitation, e.g., increases at l ate (>0.5-1 h) periods after tetanus. Calculations of partial correlat ions and regression analysis indicated that positive correlation betwe en potentiation magnitude and initial (pretetanic) paired-pulse facili tation tended to increase in the late potentiation phase (1.5-2.5 h po st-tetanus) indicating that different mechanisms are involved in the e arly (0.5 h post-tetanus) and the late phase of long-term potentiation . The findings are compatible with involvement of presynaptic mechanis ms in both the early and late phases of long-term potentiation. Howeve r, the results suggest that contribution of changes in release probabi lity and in effective number of transmitter release sites may differ d uring the two phases. II is suggested that activation of silent synaps es and increases in the number of transmission zones due to pre- and p ostsynaptic structural rearrangements represent important mechanisms o f the late phase of long-term potentiation. (C) 1998 IBRO. Published b y Elsevier Science Ltd.