ACTIVITY-MEDIATED CHANGES IN FEEDFORWARD INHIBITION IN THE DENTATE COMMISSURAL PATHWAY - RELATIONSHIP TO EPSP SPIKE DISSOCIATION IN THE CONVERGING PERFORANT PATH

1. We tested the hypothesis that long-term synaptic potentiation (LTP)-associated excitatory postsynaptic potential (EPSP)/spike dissociation in the dentate gyrus (DG) is determined, in part, by changes in the feed-forward inhibition evoked by perforant path (PP) stimulation. The dentate commissural pathway (CP) and the PP activate a common pool of interneurons. Therefore a change in synaptic efficacy in the inhibitory circuit due to activation of one pathway could lead to changes in inhibitory efficacy in the other. The relationship between changes in feed-forward inhibition in the CP and EPSP/spike (E-S) functions in the PP should provide information about the site (s) of synaptic modification. 2. In urethan-anesthetized rats, we measured the inhibition of evoked PP population spikes by the CP at interstimulus intervals of 6 and 12 ms. This measure of commissural inhibition and conventional E-S functions for the PP input to the DG were obtained before and after 1) PP tetany (400 Hz, 8-pulse trains) at low, medium, and high stimulus intensities, and 2) CP tetany (200 Hz, 7-pulse trains). 3. Low-intensity PP conditioning (just above population spike threshold) led to a decrease in CP inhibition and large left shifts of the E-S function. High- and medium-intensity PP conditioning yielded increases in commissural inhibition and smaller leftward E-S shifts. 4. Commissural conditioning led to increases in commissural inhibition and inconsistent changes in the E-S functions. Post-hoc analysis revealed that in the CP tetany cases leftward shifts of the E-S curves accompanied depression of the PP population EPSP (range 0 to - 9%) and rightward shifts accompanied slight potentiation of the PP pEPSP (range 2.3-9%). 5. The results show that the disynaptic inhibitory circuit in the DG can express activity-mediated plasticity and that changes in this circuit occur under conditions that alter the E-S relationship. This suggests that changes in inhibition contribute to, but may not completely account for, changes in the E-S relationship.