Fig. 4. Perforant path synaptic transmission is augmented by activation of kainate receptors. A,Bottom, A representative recording from a wild-type CA3 neuron demonstrating that amplitudes of evoked perforant path EPSCs were increased and failures were decreased reversibly during kainate application. Top, Representative EPSCs. EPSCs were evoked at 0.1 Hz frequency by monopolar stimulation in the stratum lacunosum moleculare. B, A representative recording from a GluR6−/− CA3 neuron demonstrating that amplitudes of evoked perforant path EPSCs were decreased during kainate application. C, A recording from a GluR5−/− CA3 neuron that showed a reduction in EPSC amplitude during kainate application. Perforant path transmission in GluR5−/− neurons showed variable responses to 3 μm kainate; four of six synaptic responses were reduced, whereas EPSC amplitudes increased in the remaining two of six recordings. D, A representative recording from a GluR5−/−/GluR6−/−CA3 neuron demonstrating that amplitudes of evoked perforant path EPSCs were unchanged during kainate application. E,Left, A diagram illustrating the slice preparation and recording configuration for perforant path stimulation.Right, Summary of the effect of application of kainate on perforant path→CA3 EPSCs. PP transmission was enhanced by +170 ± 74% in wild-type mice. GluR5−/− neurons had variable responses to kainate—in four of six recordings kainate reduced EPSC amplitudes by −38.9 ± 3.9%, but in two neurons the amplitudes were increased by +44.9 and +113.3%. The mean for all six recordings, −5.2 ± 23.2%, is shown in the histogram. The mean change in GluR6−/− EPSC amplitudes was −38.1 ± 8.1%. Finally, GluR5−/−/GluR6−/−mice showed little change in amplitude during kainate application (+1.2 ± 6.6%). mGluRs activation with L-CCG-1 did not reduce associational-commissural transmission in these recordings. Calibration: A, x-axis, 32.5 msec;y-axis, 300 pA; B, x-axis, 32.5 msec; y-axis, 150 pA; C,x-axis, 32.5 msec; y-axis, 150 pA;D, x-axis, 32.5 msec;y-axis, 300 pA.