EFFECTS OF IN-SITU MANIPULATION OF NITRIC-OXIDE ON RAT HIPPOCAMPAL CA3 NEURON EXCITABILITY

THE response of hippocampal CA3 neurones to commissural stimulation, a s expressed by the orthodromic population spike (PS2) recorded in anae sthetized rats, was increased when the recording micropipette containe d the nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginine me thyl ester (20 mM). The increase was stable upon repeated stimulation. When the recording micropipette contained the NO donor sodium nitropr usside (SNP; 10 mM) the amplitude of PS2 elicited by low and middle st imulus strength (I-stim) rapidly decreased, while remaining unchanged at higher I-stim. When the SNP-containing microelectrode was maintaine d in place for longer, the depression of PS2 observed at low and mediu m I-stim disappeared and PS2 increased at high I-stim. This long-term SNP-induced increase in PS2 at high I-stim was reduced by pretreatment with cycloheximide (5 mg kg(-1), i.p.). These data, which provide the first demonstration that in situ manipulation of NO produces dual eff ects on neuronal responsiveness in a highly seizure-prone brain region , suggest that tonic levels of endogenous NO reduce the excitability o f CA3 pyramidal neurones, whereas long-term overexposure to NO causes hyperexcitability possibly via genomic mechanisms.