Effect of atropine and PCPA on the behavioral modulation of paired-pulse response in the hippocampal CA1 region.

This study investigated the effect of cholinergic and serotonergic inputs on the paired-pulse response in hippocampal CA1 region of behaving rats. Paired-pulses were delivered to the Schaffer collaterals, at an interpulse interval (IPI) of 30 ms, and field responses were recorded at the proximal CA1 apical dendritic layer. Previously, paired-pulse facilitation of the CA1 population spike was shown to be significantly larger during walking than immobility. The muscarinic cholinergic antagonist, atropine sulfate (50 mg/kg i.p.), strongly attenuated this paired-pulse facilitation during walking at given amplitude of the population spike evoked by the first pulse. Parachlorophenylalanine (PCPA; 100 mg/kg i.p. for 3 days), an inhibitor of serotonin synthesis, alone did not change paired-pulse facilitation and the combined action of PCPA and atropine resembled that of atropine alone. The excitatory postsynaptic potentials did not change significantly with behavior or after drugs. Thus, we have shown that the behaviorally dependent modulation of paired-pulse response in the CA1 region is mediated primarily by a cholinergic and not a serotonergic input.