[Neural mechanism underlying generation of synchronous oscillations in hippocampal network]

The hippocampus, which is known as the center for learning and memory, is a remarkable neural structure that displays a variety of synchronous oscillations under physiological or pathophysiological conditions, such as theta rhythms, ripples, and epileptic seizures. Epileptic seizures, in particular, are caused by the enormous synchronous and rhythmic firing of hippocampal neurons (2-5 Hz) and can last for up to several minutes in temporal lobe epilepsy. Electrically induced seizure-like afterdischarges are an excellent experimental system for elucidating the network mechanisms underlying the neuronal synchronization and rhythm generation of these epileptic seizures in extremely hyperactive hippocampal networks. In this paper, we review the key findings of recent in vitro studies on the seizure-like afterdischarge in a local neuronal network in the rat hippocampal CA1 area. During the afterdischarge, GABAergic synaptic transmissions become transiently depolarizing and even excitatory as chloride rapidly accumulates post-synaptically through the GABAA receptors on hippocampal pyramidal cells. This transient GABAergic excitation is enhanced by glutamate release and extracellular potassium accumulation. Dual whole-cell patch-clamp recordings from a variety of interneurons and their neighboring pyramidal cells revealed that interneurons located in the stratum oriens and stratum pyramidale, including basket, chandelier, and bistratified cells, exhibited prominent firing activity that was phase-locked to the afterdischarge responses in the pyramidal cells. Thus, neuronal synchronization during the afterdischarge is achieved by synergistic excitations of glutamatergic pyramidal cells and GABAergic interneurons. Our observations also suggest that local circuits in the stratum oriens and stratum pyramidale may be responsible for rhythmic excitation during the seizure-like afterdischarge; however the detailed mechanism underlying this rhythmic excitation is not yet fully understood.