Voltage imaging reveals the CA1 region at the CA2 border as a focus for epileptiform discharges and long-term potentiation in hippocampal slices

Abstract

Voltage-sensitive-dye imaging was used to study the initiation and propagation of epileptiform activity in transverse hippocampal slices. A portion of the slices tested generated epileptiform discharges in response to electrical shocks under normal physiological conditions. The fraction of slices showing epileptiform responses increased from 44 to 86% when bathing [K+] increased from 3.2 to 4 mM. Regardless of stimulation site in the dentate gyrus and hippocampus, discharges generally initiated in the CA3 region. After onset, discharges abruptly appeared in the CA1 region, right at the CA2 border. This spread from the CA3 region to the CA1 region was saltatory, occurring before detectable activity in the intervening CA2 and CA3 regions. Discharges did eventually propagate smoothly through the intervening CA3 region into the CA2 region, but on a slower timescale. The surge in the CA1 region did not spread back into the CA2 region, but spread through the CA1 region toward the subiculum. Tetanic stimulation, theta bursts, and GABA(A) receptor antagonists failed to alter this characteristic pattern, but did reduce the latency of discharge onset. The part of the CA1 region at the CA2 border, where epileptic responses emerged with relatively short latency, also expressed stronger long-term potentiation (LTP) than the rest of the CA1 region. The CA2 region, where discharges had long latencies and low amplitudes, expressed weaker LTP. Thus the CA1 region at the CA2 border has unique properties, which make this part of the hippocampus an important locus for both epileptiform activity and plasticity.