Impairment of kindling development in phospholipase Cγ1 heterozygous mice

ObjectiveElucidating molecular mechanisms underlying limbic epileptogenesis may reveal novel targets for preventive therapy. Studies of TrkB mutant mice led us to hypothesize that signaling through a specific phospholipase (PLC), PLC1, promoted development of kindling. MethodsTo test this hypothesis, we examined the development of kindling in PLC1 heterozygous mice. We also examined the cellular and subcellular location of PLC1 in adult wild-type mice. ResultsThe development of kindling was impaired in PLC1 heterozygous mice compared to wild-type controls. PLC1 immunoreactivity was localized to the soma and dendrites of both excitatory and inhibitory neurons in the hippocampus of adult mice. SignificanceThis study implicates PLC1 signaling as the dominant pathway by which TrkB activation promotes limbic epileptogenesis. Its cellular localization places PLC1 in a position to modify the efficacy of both excitatory and inhibitory synaptic transmission. These findings advance PLC1 as a novel target for therapies aimed at preventing temporal lobe epilepsy induced by status epilepticus.