HYPEREXCITABILITY IN CA(1) OF THE RAT HIPPOCAMPAL SLICE FOLLOWING HYPOXIA OR ADENOSINE

Participation of adenosine receptors in the depression of synaptic tra nsmission during hypoxia, and the production of multiple populations s pikes in the pyramidal neurons following hypoxia, has been investigate d in the CA(1) area of the rat hippocampal slice. A method is presente d for analysing such hyperexcitability, using input/output curves of t he second population spike. This method provides evidence that rebound hyperexcitability following hypoxia or prolonged adenosine-mediated i nhibition results from an increase in excitability of the CA(1) pyrami dal neurons rather than from an increase in excitatory neurotransmitte r release. Hypoxia-induced depression of the synaptic components of ev oked field potentials was blocked in a concentration dependent manner by the selective A(1) receptor antagonist 8-cyclopentyltheophylline (8 -CPT), demonstrating extracellular accumulation of adenosine during hy poxia. Upon reoxygenation of slices following 30 min hypoxia, multiple population spikes were evoked by a single orthodromic stimulus in sli ces that exhibited only a single population spike prior to hypoxia. Su ch post-hypoxic hyperexcitability was not prevented by superfusion of slices with 8-CPT during hypoxia. Depression of synaptic transmission by 30 min superfusion of slices with 50 mu M adenosine was also follow ed, upon washout, by the appearance of multiple population spikes. How ever, such hyperexcitability could not be produced by superfusion with adenosine analogues selective for A(1) receptors, cyclopentyladenosin e, selective for A(2a) receptors, ethyl)phenetheylamino-5'-ethylcarbox amidoadenosine (CGS 21680), or active at A(2a) and A(2b) receptors, im ethoxyphenyl)-2-(2-methylphenyl)ethyl]adenosine, suggesting that adeno sine receptors other than the A(1), A(2a) or A(2b) subtypes are involv ed in its generation.