Effects of lidocaine reversible inactivation of the median raphe nucleus on long-term potentiation and recurrent inhibition in the dentate gyrus of rat hippocampus

Abstract

Considering the fact that median raphe nucleus (MRN) constitutes one of the inputs of the hippocampus, the effects of reversible inactivation of MRN on long-term potentiation (LTP) and recurrent inhibition in the dentate gyrus (DG) of rat hippocampus, in vivo, were examined. Rats were anesthetized with urethane (1.5 g/kg, i.p.). MRN was temporarily suppressed by intra-MRN injection of lidocaine (0.5 microl, 2%). For LTP induction, eight episodes of high frequency stimuli (100 Hz) were delivered to the perforant path (PP), each consisting of 10 stimuli at 100 Hz. Population spikes (PS) and population excitatory post synaptic potentials ((P)EPSP) in DG were recorded 10 min before, and 5, 10, 20, 40, 60 and 120 min after tetanization. MRN inactivation itself had no effect on the amplitude of baseline responses. The PS amplitude and (P)EPSP slope in rats, injected with intra-MRN lidocaine, 5 min before tetanization, were not different from the control group. However, at 120 min PS amplitude was significantly higher than control. Lidocaine injection 5 min after tetanic stimuli caused a significant decrease in PS amplitude (10, 20 and 60 min) and (P)EPSP slope (20 and 40 min) after tetanization. The data showed that inactivation of MRN has no effect on LTP induction in the DG of hippocampus but it does affect its maintenance, and this effect depends on the pre- or post-tetanic inactivation. In the last part of this study, in order to investigate the effect of MRN on the efficacy of recurrent inhibition in the perforant-dentate synapses, paired pulse was applied to the PP at 10 and 20 ms interpulse intervals. Inactivation of MRN increased the amount of recurrent inhibition in the DG with 20 ms interpulse interval. This observation indicates that MRN inhibits the recurrent inhibition mechanism, which is in accordance with the suggested role of MRN neurons on inhibition of hippocampal GABAergic interneurons.