Modulation of paired-pulse activation in the hippocampal dentate gyrus by cholecystokinin, baclofen and bicuculline.

Paired-pulse stimulation was used to evaluate the effects of the sulfated octapeptide of cholecystokinin (CCK8-S), the gamma-aminobutyric acidB (GABAB) agonist (-) baclofen, and the GABAA antagonist (-) bicuculline on hippocampal dentate gyrus (DG) granule cell excitability. Evoked action potentials (EAPs) and excitatory postsynaptic potentials (EPSPs) were recorded in response to orthodromic stimulation of the medial (MPP) or lateral (LPP) perforant pathway. Paired-pulse indices were determined using interpulse intervals (IPIs) across the range of 5-1000 ms. As reported by others, three phases of paired-pulse effects were revealed under control (drug-free ACSF) conditions: early paired-pulse inhibition (PPI), intermediate paired-pulse facilitation (PPF) and late PPI. With EAPs, CCK8-S enhanced only the intermediate PPF on both pathways, with no effect on the early or late PPIs. The effects of (-) baclofen were similar to CCK8-S. (-) Bicuculline attenuated the early and late PPI as well as the PPF. No differences were measured on the MPP- or LPP-evoked EPSPs in any of the drug conditions. These results indicate a similarity of CCK8-S- with GABAB-mediated modulation on neuronal activation in the DG. CCK8-S disinhibition of DG granule cells may play a role in the induction of long-lasting synaptic modifications.