Abstract
OBJECTIVE: Elucidating 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), PLCγ1, promoted development of kindling. METHODS: To test this hypothesis, we examined the development of kindling in PLCγ1 heterozygous mice. We also examined the cellular and subcellular location of PLCγ1 in adult wild-type mice. RESULTS: The development of kindling was impaired in PLCγ1 heterozygous mice compared to wild-type controls. PLCγ1 immunoreactivity was localized to the soma and dendrites of both excitatory and inhibitory neurons in the hippocampus of adult mice. SIGNIFICANCE: This study implicates PLCγ1 signaling as the dominant pathway by which TrkB activation promotes limbic epileptogenesis. Its cellular localization places PLCγ1 in a position to modify the efficacy of both excitatory and inhibitory synaptic transmission. These findings advance PLCγ1 as a novel target for therapies aimed at preventing temporal lobe epilepsy induced by status epilepticus.