Development of NMDA-induced theta rhythm in hippocampal formation slices

During the past 20 years experimental evidence has accumulated demonstrating that the appearance of theta rhythm requires a certain level of excitation of local neuronal networks. In this study we extended our earlier in vitro observations concerning the involvement of cholinergic and GABAergic neurotransmission in hippocampal theta production. Specifically, we investigated whether the hippocampal neuronal network is capable of generating theta oscillations in the presence of N-methyl-d-aspartic acid (NMDA) in a brain slice preparation. To answer this question, the effect of different concentrations of NMDA (Experiment I) and the effect of interaction between NMDA and GABA_A/_B agonists and antagonists on field potentials recorded in the CA3c region of hippocampal formation (HPC) slice preparations (Experiment II) was examined. We demonstrated for the first time that apart from the epileptiform activity recorded in almost all series of Experiments I and II, only the perfusion of HPC slices with NMDA in doses of 30 and 50 μM, as well as the perfusion of HPC slices with NMDA and GABA_B agonist baclofen (50 μM NMDA + 50 μM BACL), resulted in the appearance of individual theta epochs. The best synchronized theta oscillations obtained after administration of 50 μM NMDA + 50 μM BACL resembled theta activity induced by a bath perfusion of 50 μM carbachol. In light of the obtained results we conclude that besides the cholinergic and GABAergic input, NMDA glutamatergic drive is also important for the appearance of theta oscillations in HPC in vitro.