Enhancement of the synchronized firing of CA1 pyramidal cells by medial septum preconditioning: Time-dependent involvement of muscarinic cholinoceptors and GABA B receptors

Abstract

Activation of the medial septum (MS) enhances the synchronized firing of pyramidal cells in the hippocampus. At least two distinct mechanisms might be recruited in this process: GABAergic inhibition of hippocampal inhibitory interneurons and cholinergic enhancement of pyramidal cell excitability. In the present study, a field potential recording in urethane anaesthetised rats was used to show that MS preconditioning with brief high-frequency burst stimulation markedly enhanced Schaffer collateral/commissural (SC/C) synaptically evoked population spikes in the CA1 area without significant alteration in the initial slope of SC/C field excitatory postsynaptic potentials (fEPSPs). An early phase (<∼125 ms) of the facilitation of neuronal discharge was inhibited by intracerebroventricular (i.c.v.) injection of the GABA B receptor antagonist CGP 52432 (200 nmol/5 μl). In contrast, the muscarinic cholinoceptor antagonist scopolamine (20 nmol/5 μl) inhibited a later phase (∼150–300 ms) of the population spike facilitation. These findings support an important role for both cholinergic and GABAergic mediated septal drive in the tuning of signal conversion within the hippocampus as well as in securing the cortical feedback from the hippocampus.