Excitability of rat dentate gyrus granule cells in vivo is controlled by tonic and evoked GABA B receptor-mediated inhibition

Abstract

Tonic or evoked γ-aminobutyric acid B (GABA B) receptor-mediated modulation of dentate gyrus excitability was evaluated in vivo in urethane-anesthetized rats. Two stimuli at an interpulse interval (IPI) of 10–9000 ms were given to the medial perforant path. Population excitatory postsynaptic potentials (pEPSPs) and population spikes (PSs) were recorded in the dentate gyrus using a glass micropipette or a multichannel silicon probe. The GABA B receptor antagonist CGP35348, delivered intracerebroventricularly (i.c.v.) or locally, caused a significant increase in the PS amplitude evoked by the first pulse (PS1) without an increase in either the slope or current sink of the population EPSP evoked by the first pulse (pEPSP1). The average spontaneous firing rate of putative granule cells was also increased following i.c.v. CGP35348. The PS evoked by the second pulse (PS2) relative to PS1 (PS2/PS1) was consistently suppressed at IPIs from 30 to 70 ms, even when PS1 was matched before and after CGP35348. CGP35348 increased PS1 mainly by blocking tonic postsynaptic GABA B receptors and decreased PS2 at 30–70 ms IPI by blocking presynaptic GABA B autoreceptors. These data suggest that GABA B receptors are tonically active in the dentate gyrus in vivo.