Effects of reversible inactivation of the medial septal area on long-term potentiation and recurrent inhibition of hippocampal population spikes in rats

Abstract

We assessed the effects of reversible inactivation of the medial septal area (MSA) on long-term potentiation (LTP) and recurrent inhibition in the dentate gyrus of urethane-anesthetized rats, in vivo. The septal input to the hippocampus was temporarily eliminated by injection of tetrodotoxin (TTX, 10 ng/1 μl) into the MSA. In Experiment 1, LTP inducibility was examined in the perforant-dentate gyrus synapses in the MSA inactivated and control rats by 2 high-frequency stimulation (HFS), 5 min apart, applied to the perforant pathway (PP). The magnitude of potentiation was evaluated as the percentage change in the population spike (PS) amplitude at 5, 30, 60 or 120 min after the second HFS. The PS amplitude in the MSA inactivated rats was significantly lower than those of control group at 120 but not 5, 30 or 60 min after the second HFS. The MSA inactivation itself had no effect on the basal responses evoked by test stimuli. In Experiment 2, the MSA inactivation did not affect the efficacy of recurrent inhibition in the perforant-dentate gyrus synapses produced by paired pulses applied to the PP at 10- and 20-ms interpulse intervals. These results indicate that: (1) although hippocampal synapses can be still potentiated after the HFS in the MSA inactivated animals, a faster decay of LTP may be due to elimination of the MSA output amplification on synaptic responses mediated by excitatory amino acids; and (2) the recurrent inhibition mechanism in the dentate gyrus of the hippocampus is not probably affected by the MSA inactivation.