TY - JOUR T1 - Disruption of TrkB-Mediated Phospholipase Cγ Signaling Inhibits Limbic Epileptogenesis JF - The Journal of Neuroscience JO - J. Neurosci. SP - 6188 LP - 6196 DO - 10.1523/JNEUROSCI.5821-09.2010 VL - 30 IS - 18 AU - Xiao Ping He AU - Enhui Pan AU - Carla Sciarretta AU - Liliana Minichiello AU - James O. McNamara Y1 - 2010/05/05 UR - http://www.jneurosci.org/content/30/18/6188.abstract N2 - The BDNF receptor, TrkB, is critical to limbic epileptogenesis, but the responsible downstream signaling pathways are unknown. We hypothesized that TrkB-dependent activation of phospholipase Cγ1 (PLCγ1) signaling is the key pathway and tested this in trkBPLC/PLC mice carrying a mutation (Y816F) that uncouples TrkB from PLCγ1. Biochemical measures revealed activation of both TrkB and PLCγ1 in hippocampi in the pilocarpine and kindling models in wild-type mice. PLCγ1 activation was decreased in hippocampi isolated from trkBPLC/PLC compared with control mice. Epileptogenesis assessed by development of kindling was inhibited in trkBPLC/PLC compared with control mice. Long-term potentiation of the mossy fiber-CA3 pyramid synapse was impaired in slices of trkBPLC/PLC mice. We conclude that TrkB-dependent activation of PLCγ1 signaling is an important molecular mechanism of limbic epileptogenesis. Elucidating signaling pathways activated by a cell membrane receptor in animal models of CNS disorders promises to reveal novel targets for specific and effective therapeutic intervention. ER -