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Impairment of kindling development in phospholipase Cγ1 heterozygous mice
Author(s) -
He Xiao Ping,
Wen Renren,
McNamara James O.
Publication year - 2014
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/epi.12536
Subject(s) - epileptogenesis , kindling , neuroscience , epilepsy , status epilepticus , hippocampus , excitatory postsynaptic potential , hippocampal formation , inhibitory postsynaptic potential , kindling model , biology
Summary Objective Elucidating molecular mechanisms underlying limbic epileptogenesis may reveal novel targets for preventive therapy. Studies of T rk B mutant mice led us to hypothesize that signaling through a specific phospholipase ( PLC ), PLC γ1, promoted development of kindling. Methods To test this hypothesis, we examined the development of kindling in PLC γ1 heterozygous mice. We also examined the cellular and subcellular location of PLC γ1 in adult wild‐type mice. Results The development of kindling was impaired in PLC γ1 heterozygous mice compared to wild‐type controls. PLC γ1 immunoreactivity was localized to the soma and dendrites of both excitatory and inhibitory neurons in the hippocampus of adult mice. Significance This study implicates PLC γ1 signaling as the dominant pathway by which T rk B activation promotes limbic epileptogenesis. Its cellular localization places PLC γ1 in a position to modify the efficacy of both excitatory and inhibitory synaptic transmission. These findings advance PLC γ1 as a novel target for therapies aimed at preventing temporal lobe epilepsy induced by status epilepticus.