Overexpression of GluR6 in rat hippocampus produces seizures and spontaneous nonsynaptic bursting in vitro

We hypothesized that overexpression of specific glutamate receptors within the hippocampus would induce seizures and the associated cellular changes s een in temporal lobe epilepsy (TLE). The GluR6 kainate receptor was overexp ressed by injecting rat hippocampi with HSVGluR6, a viral vector transducin g fully edited GluR6, These animals experienced limbic seizures approximate ly 4 h following the injection, Control animals injected with HSVlac, a vec tor expressing beta-galactosidase, did not have seizures. Recordings from h ippocampal CA1 pyramidal cells were performed 12 to 48 h and 1 week to 1 mo nth postinjection. We observed nonsynaptic Na C-mediated bursting in 77.5% of cells 12 to 48 h following injection of HSVGluR6 but not HSVlac, The syn aptic responses were normal in both groups. However, the physiological prop erties of cells from HSVGluR6-injected hippocampi changed over time. Two we eks following HSVGluR6 injection, synaptic bursts could be evoked, but intr insic bursting became rare. These changes persisted for at least 1 month. W e postulate that this transition from intrinsic to synaptic hyperexcitabili ty may be important in the development of TLE. (C) 2000 Academic Press.