Changes in neuronal excitability and synaptic function in a chronic model of temporal lobe epilepsy.
Long-term potentiation and depression of glutamatergic synaptic responses are accompanied by an increased firing probability of neurons in response to a given excitatory input. This property, named excitatory postsynaptic potential/spike potentiation, has also been described in epileptic tissue and has pro-epileptic consequences. In this study, we show that excitatory postsynaptic potential/spike potentiation can be reversed in the kainic acid lesioned rat hippocampus, a chronic model of temporal lobe epilepsy. Simultaneous in vitro extracellular recordings in stratum radiatum and stratum pyramidale were performed in the CA1 area of the kainic acid lesioned rat hippocampal slices. Fifteen minutes, application of the K(+) channel blocker tetraethylammonium resulted in excitatory postsynaptic potential/spike potentiation (measured 90min after the start of the washout period) which could be reversed by subsequent low-frequency or tetanic stimuli. Excitatory postsynaptic potential/spike potentiation and its subsequent reversal by an electrical conditioning stimulus were found to have a N-methyl-D-aspartate receptor-independent component. Tetraethylammonium treatment also resulted in excitatory postsynaptic potential/spike potentiation of pharmacologically isolated N-methyl-D-aspartate receptor-mediated responses which could be reversed by subsequent low-frequency or tetanic stimuli. We conclude that excitatory postsynaptic potential/spike potentiation can be reversed in epileptic tissue, even in the absence of synaptic plasticity. These results suggest the presence of endogenous regulatory mechanisms which are able to decrease cell excitability.
Bernard
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Centre for Neuroscience, School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton, SO16 7PX, UK.
Marsden
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DP
Wheal
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HV
D000200:Action Potentials; D000818:Animals; D002908:Chronic Disease; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology*; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus; D007608:Kainic Acid; D017774:Long-Term Potentiation; D026902:Potassium Channel Blockers; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D019789:Tetraethylammonium
D026902:Potassium Channel Blockers; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D019789:Tetraethylammonium; D007608:Kainic Acid