A study of the transition from spindles to spike and wave discharge in feline generalized penicillin epilepsy: microphysiological features.
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G Kostopoulos
Publications and source records attributed to G Kostopoulos.
Increased postsynaptic excitability in hippocampal slices from the tottering epileptic mutant mouse.
The tottering mouse exhibits an inherited form of generalized epilepsy, which can be characterized by electroencephalographic, behavioral and pharmacological criteria as belonging to the 'absence' type. In vitro electrophysiological experiments in hippocampal slices revealed a higher than normal postsynaptic excitability in slices from epileptic mice. Upon stimulation of Schaffer collaterals, we obtained input/output curves from the CA1 pyramidal cell layer and determined several indices of synaptic activation and postsynaptic excitability. Only the latter were found to be statistically different: population spikes were elicited by relatively smaller field EPSPs (P less than 0.001) in the slices from epileptic mice. However, their maximum population spike was significantly smaller, which indicated that fewer neurons were available for firing. In the normal but not in the epileptic mice in vitro postsynaptic excitability was correlated to the age of the animal.
Action Potentials↗
Caffeine blocks absence seizures in the tottering mutant mouse.
The neurological tottering mutant mouse is characterized by frequent "absence" seizures accompanied by bilateral synchronous spike and wave EEG bursts. Under anesthesia, adult homozygous tottering mice were implanted with permanent epidural electrodes, and at least 7 days elapsed before electrocorticograms in unrestrained mice were scored for seizure incidence and duration. Caffeine (5, 10, 15 mg/kg, n = 8) injected intraperitoneally (i.p.) at the fourth hour of 8-h recording sessions significantly (p less than 0.001 for 10 and 15 mg) decreased seizure incidence as compared with control saline injections. Spike and wave bursts were eliminated during the 30 min after injection and reached 50% preinjection levels between the first and the second hour after injection. Another central nervous system (CNS) stimulating drug, amphetamine (1 mg/kg; n = 5), under identical conditions failed to decrease seizure incidence in this mutant.
Amphetamine↗
Comparison of the effects of increased potassium and of adenosine on hippocampal neurons from normal and genetically epileptic tg/tg mice.
Tottering mice are an experimental model of genetically determined generalized epilepsy of the absence type. We investigated possible mechanisms underlying epileptogenic hyperexcitability in these mice by studying input/output (I/O) curves of the extracellular response of CA1 neurons to stratum radiatum stimulation in hippocampal slices maintained in vitro. Increases in extracellular potassium are considered to contribute to epileptogenesis, whereas adenosine has been proposed to be an endogenous antiepileptic agent. Moderate elevations (+2 mM) of extracellular K+ concentrations induced a significantly smaller increase of this response (leftward shift of the input/output curves) in slices from epileptic mice as compared with controls. Perfusion of slices with adenosine 10 microM decreased excitability in both groups of slices, especially with regard to response threshold. Adenosine more effectively decreased the responses elicited by low-intensity stimulation than those elicited by high intensity. No significant difference between the groups of slices was observed. On the basis of the present data, it is unlikely that the previously observed hyperexcitability of hippocampal neurons of tottering mice results from a genetically altered sensitivity to moderate increases in [K+]o or to adenosine.
Adenosine↗
Pentylenetetrazol-induced seizures decrease gamma-aminobutyric acid-mediated recurrent inhibition and enhance adenosine-mediated depression.
To elucidate the consequences of convulsions, we examined biochemically and electrophysiologically the brains of mice that had sustained two complete tonic-clonic convulsions after administration of pentylenetetrazol (PTZ 50 mg/kg intraperitoneally, i.p.), 48 and 24 h before decapitation. Control mice were injected with saline. Input/output curves of the extracellular synaptic responses in the CA1 area of hippocampal slices showed that PTZ-induced seizures do not establish the persistent change in hippocampal excitability itself that can be detected in vitro. However, use of the paired-pulse stimulation paradigm showed that gamma-aminobutyric acid A (GABAA)-mediated recurrent inhibition was significantly weaker (by 19-25%) in the CA1 area of slices from PTZ-treated mice (PTZ slices) as compared with slices from control mice (control slices). The density of GABAA receptors (high-affinity component) was also lower in hippocampus (by 19%) and cortex (by 14%) of PTZ-treated mice. A GABA-related disinhibitory mechanism underlying PTZ seizures may thus persist for 1 day after the seizure, predisposing the brain to subsequent seizures. On the other hand, the depressant effect of a single dose of adenosine 10 microM on the CA1 synaptic response was stronger (by 35% on population spikes) and longer lasting in PTZ slices as compared with controls. This could be attributed to significantly higher adenosine A1 receptor density in hippocampus (Bmax of [3H]CHA was higher by 34%) as well as cortex and cerebellum of these animals. The phenomenon may reflect an adenosine A1-mediated adaptive mechanism that offers protection from subsequent seizures.
Action Potentials↗