Epileptogenic insult alters endogenous adenosine control on long-term changes in synaptic strength by theta pattern stimulation in hippocampus area CA1.

The impact of theta patterning of the stimulation on the kindling effects of pentylenetetrazol (PTZ) was studied in rat hippocampus area CA1 in vitro. A potential involvement of adenosine A1 receptors was also examined. Primed-bursts stimulation (PBs) and theta pulse stimulation (TPS) were used as patterned activities. Stimulus patterns were applied to the Schaffer collateral afferents of hippocampal slices from both control and PTZ-kindled rats, the field excitatory postsynaptic potentials (fEPSP) and population spikes (PS) were simultaneously recorded from stratum radiatum and stratum pyramidale, respectively. Experiments were carried out in the presence or absence of the adenosine A1 receptor antagonist CPX. The following changes in kindled vs. control slices were observed. PBs was unable to produce both fEPSP LTP and PS LTP in untreated slices. When A1 receptor antagonist CPX was applied before PBs, both fEPSP LTP and PS LTP were elicited. PS LTP was selectively depressed by TPS (applied at 60 min after LTP induction) exclusively when A1 receptors were blocked, while TPS failed to depress PS LTP in untreated PBs-exposed slices. These findings suggest that seizing entails lasting changes in hippocampus area CA1 so that LTP induction by PBs is masked due to intensive adenosine release which in turn prevents TPS to induce PS LTD in epileptic CA1 network.