Postsynaptic expression of long-term potentiation in the rat dentate gyrus demonstrated by variance-mean analysis

1. Long-term potentiation (LTP) of synaptic transmission is the putative mechanism underlying learning and memory. Despite intensive study, it remains controversial whether LTP is expressed at a pre- or postsynaptic locus. A new approach was used to investigate this question at excitatory synapses from the medical perforant path (MPP) onto granule cells in the hippocampal dentate gyrus. The variance of the evoked synaptic amplitude was plotted against mean synaptic amplitude at several different Cd2+ concentrations. The slope of the variance-mean plot estimates the average amplitude of the response following the release of a single vesicle of transmitter Q(av). A presynaptic modulation should not affect Q(av), but a postsynaptic modulation should alter it. 2. The variance-mean technique was tested by applying the analysis before and after three different synaptic modulations: (i) a reduction in Q(av) by the addition of the competitive antagonist CNQX; (ii) a reduction in the average probability of transmitter release P(av) by the addition of baclofen; and (iii) an increase in the number of active synaptic terminals (N) by increasing the stimulus strength. CNQX reduced the average synaptic amplitude and Q(av) to the same extent, consistent with a postsynaptic action. In contrast, neither a change in N nor P(av) altered Q(av). This confirms that the variance-mean technique can distinguish between a pre- and postsynaptic site of modulation. 3. Induction of LTP increased EPSC amplitude by 50 ± 0.4% (n = 5) and, in the same cells, increased Q(av) by 47 ± 0.6%. There was no significant difference between the increase in EPSC amplitude and the increase in Q(av). Thus, LTP of the MPP input to dentate granule cells can be explained by an increase in the postsynaptic response to transmitter