Ontogeny of altered synaptic function in a rat model of chronic temporal lobe epilepsy.
In the limbic status model of chronic temporal lobe epilepsy, hippocampal stimulation induces acute status epilepticus in rats; recurrent, spontaneous seizures develop following an asymptomatic silent period lasting several weeks. Previous work has shown increased excitability and decreased inhibition in CA1 pyramidal neurons in chronically epileptic animals. To determine the relationship of altered cellular responses to seizure onset, in vitro intracellular recording was used to follow the evolution of changes in synaptic physiology occurring during the seizure-free silent period. Pyramidal cells displayed increasing epileptiform activity throughout the period investigated, 3-14 days following status; the mean number of evoked action potentials from 1.1+/-0.05 in control cells to 2.4+/-0.4 early (3 days after status) and 4. 3+/-0.7 late (14 days) in the silent period. Monosynaptic inhibitory postsynaptic potentials mediated by gamma-aminobutyric acid-A receptors in silent period cells differed markedly from controls. Area, rise time, and duration of these potentials decreased by 40-60% within 3 days following status and to values commensurate with chronically epileptic animals in 7 to 10 days. gamma-Aminobutyric acid-B receptor-mediated IPSPs diminished more gradually in the silent period, reaching a minimum at day 14. In contrast, presynaptic gamma-aminobutyric acid-B receptor function showed maximum impairment 3 days after status. The benzodiazepine type 1 receptor agonist zolpidem reduced hyperexcitability in both silent period and chronically epileptic cells, but was more effective at unmasking the underlying IPSP in silent period neurons. The results indicate that changes in different components of pyramidal cell inhibitory synaptic physiology associated with chronic epilepsy in this model evolve individually at different rates, but are all complete before seizure onset. Although the results do not imply causality, they do suggest that the development of physiological changes in CA1 pyramidal cells may contribute to the lag period preceding the onset of chronic seizures.
Mangan
P S
PS
Department of Neurology, Box 394, University of Virginia Health Sciences Center, Charlottesville, VA 22908, USA.
Bertram
E H
EH
D000818:Animals; D002908:Chronic Disease; D004594:Electrophysiology; D004833:Epilepsy, Temporal Lobe / Q000473:pathology / Q000503:physiopathology*; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D017729:Presynaptic Terminals / Q000378:metabolism; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000502:physiology; D018080:Receptors, GABA-B / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D013997:Time Factors; D000077334:Zolpidem
D011725:Pyridines; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D000077334:Zolpidem