Possible mechanisms underlying hyperexcitability in the epileptic mutant mouse tottering.
Tottering mice present a useful experimental model of genetically determined generalized epilepsy of the absence type. In electrophysiological recordings from hippocampal slices in vitro we found that the postsynaptic excitability (firing threshold) of pyramidal neurons in the CA1 area of tg/tg slices was significantly higher than that of normal slices. In spite of this hyperexcitability, in vitro epileptiform discharges were not observed spontaneously, or upon provocation by intracellular depolarizing pulses, or in response to moderate elevations (+2 mM) in extracellular potassium. The latter elevations actually induced significantly smaller increases in the CA1 synaptic responses of tg/tg as compared to normal slices. The hyperexcitability of tottering neurons could not be explained in terms of altered membrane electrical properties or any reduction of synaptic inhibition or increased capacity for long-term potentiation. Responses to noradrenaline, histamine and adenosine, as well as to the release of N-methyl-D-aspartate channels--by eliminating Mg(2+)--were comparable in tg/tg and normal slices. These studies show that hyperexcitability can be co-inherited with epilepsy and in this model its expression can be maintained in vitro. The neuronal mechanism of this expression remains elusive, as it does not appear to include some features known to be shared by experimental models of chemically or electrically induced epilepsy.
Kostopoulos
G K
GK
Department of Physiology, University of Patras Medical School, Greece.
Psarropoulou
C T
CT
D000818:Animals; D004195:Disease Models, Animal; D004832:Epilepsy, Absence / Q000503:physiopathology*; D005071:Evoked Potentials / Q000187:drug effects; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008818:Mice, Neurologic Mutants / Q000235:genetics; D018377:Neurotransmitter Agents / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology
D018377:Neurotransmitter Agents; D011188:Potassium