GABAergic mediation of hippocampal theta rhythm induced by stimulation of the vagal nerve

The key question to be answered in the present study was whether the medial septal GABAergic receptors are engaged in the pharmacological profile of the hippocampal formation (HPC) theta rhythm induced by vagal nerve stimulation (VNS). It was demonstrated that the medial septal microinfusion of GABA(A) and GABA(B) agonists (muscimol and baclofen) resulted in a progressive reduction of the power of VNS-induced theta. The medial septal microinfusion of GABA(A) and GABA(B) antagonists (bicuculline and 2-OH saclofen) resulted in the generation of VNS-induced theta with increased power. The effect of the combined medial septal microinfusion of GABA(A) agonist and antagonist and GABA(B) agonist and antagonist on VNS-induced theta rhythm was also evaluated: in the presence of GABA(A,B) antagonists the effect of agonists predominated. In separate experiments, GABA(A) and GABA(B) antagonists were administrated in anesthetized rats pretreated with i.v. administration of atropine sulfate. Atropine was found to abolish spontaneous theta and VNS-induced theta examined in the presence of bicuculline or 2-OH saclofen. The present data provide evidence that the medial septal GABA(A) and GABA(B) receptors are involved in the central mechanisms responsible for modulation of VNS-induced HPC theta oscillations. Furthermore, the results of the present study also demonstrate that, in fact, both GABAergic and cholinergic involvement is necessary for the appearance of VNS-induced theta.