Full-Length Original Research
Impairment of kindling development in phospholipase Cγ1 heterozygous mice
Article first published online: 6 FEB 2014
Wiley Periodicals, Inc. © 2014 International League Against Epilepsy
Volume 55, Issue 3, pages 456–463, March 2014
How to Cite
Epilepsia, 55(3):456–463, 2014
- Issue published online: 13 MAR 2014
- Article first published online: 6 FEB 2014
- Manuscript Accepted: 13 DEC 2013
- NINDS. Grant Numbers: NS56217, NS060728
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.
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.
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.
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.