MODULATION OF SYNAPTIC TRANSMISSION AND LONG-TERM POTENTIATION - EFFECTS ON PAIRED-PULSE FACILITATION AND EPSC VARIANCE IN THE CA1 REGION OF THE HIPPOCAMPUS

1. Whole-cell patch-clamp recordings of excitatory postsynaptic currents (EPSCs) were made from guinea pig hippocampal CA1 pyramidal cells. The sensitivity of paired pulse facilitation (PPF) and EPSC variance to changes in synaptic transmission was investigated and the results were compared with the changes in these parameters evoked by long-term potentiation (LTP). 2. Presynaptic manipulations, such as activation of presynaptic gamma-aminobutyric acid-B receptors by baclofen, blockade of presynaptic adenosine receptors by theophylline, blockade of presynaptic potassium channels by cesium, and increasing the Ca2+-Mg2+ ratio in the external recording solution, each reliably changed PPF in a fashion reciprocal to the change in the EPSC amplitude. However, recruitment of additional synaptic release sites by increasing stimulus strength and antagonism of non-N-methyl-D-aspartate (NMDA) glutamate receptors by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) failed to alter PPF. 3. Presynaptic manipulations including increased stimulus strength gave the predicted changes in the value of mean2/variance (M2/sigma2). Moreover, postsynaptic manipulations that altered EPSC amplitude, including blockade of non-NMDA receptors by CNQX, or changing the holding potential of the postsynaptic cell, gave little change in M2/sigma2, as would be predicted for manipulations resulting in a uniform postsynaptic change. 4. LTP caused no change in PPF, whereas the presynaptic manipulations, which caused a similar amount of potentiation to that induced by LTP, significantly decreased PPF. On the other hand, LTP did increase M2/sigma2, although the increase was less than that predicted for a purely presynaptic mechanism. 5. The results presented in this study are consistent with a postsynaptic mechanism for LTP expression in which there is a nonuniform change in postsynaptic sensitivity. They also indicate that expression of LTP results in changes in synaptic efficacy that are fundamentally different from those induced by presynaptic manipulations considered to affect primarily the probability of transmitter release. However, the data are also consistent with the idea that LTP might arise from a selective increase in the number of active synapses.