Differential Effects of Short- and Long-Term Potentiation on Cell Firing in the CA1 Region of the Hippocampus

Long-term potentiation (LTP) in the hippocampus enhances the ability of a stimulus to produce cell firing, not only by increasing the strength of the EPSPs, but also by increasing the efficiency of the input/output (I/O) function of pyramidal neurons. This means that EPSPs of a given size more easily elicit spikes after LTP, a process known as EPSP-spike (E-S) potentiation. In contrast to LTP, it is not known whether the synaptic strengthening produced by paired-pulse facilitation (PPF) also results in changes in the I/O function. We have addressed this question by examining E-S curves from rat hippocampal area CA1 in response to both PPF and LTP. We describe a novel form of I/O modulation in which PPF produces E-S depression; that is, the E-S curve is shifted to the right, indicating a decreased ability of EPSPs to elicit action potentials. Consistent with the notion that E-S potentiation observed with LTP is caused by long-term increases in the excitatory–inhibitory ratio, we show that PPF-induced E-S depression relies on short-term decreases in this ratio. These results indicate that different forms of synaptic plasticity that produce the same degree of EPSP potentiation can result in dramatically different effects on cell firing, because of the dynamic changes in the excitatory–inhibitory balance within local circuits.