Overexpression of GluR6 in Rat Hippocampus Produces Seizures and Spontaneous Nonsynaptic Bursting in Vitro

Abstract

We hypothesized that overexpression of specific glutamate receptors within the hippocampus would induce seizures and the associated cellular changes seen in temporal lobe epilepsy (TLE). The GluR6 kainate receptor was overexpressed by injecting rat hippocampi with HSVGluR6, a viral vector transducing fully edited GluR6. These animals experienced limbic seizures approximately 4 h following the injection. Control animals injected with HSVlac, a vector expressing β-galactosidase, did not have seizures. Recordings from hippocampal CA1 pyramidal cells were performed 12 to 48 h and 1 week to 1 month postinjection. We observed nonsynaptic Na⁺-mediated bursting in 77.5% of cells 12 to 48 h following injection of HSVGluR6 but not HSVlac. The synaptic responses were normal in both groups. However, the physiological properties of cells from HSVGluR6-injected hippocampi changed over time. Two weeks following HSVGluR6 injection, synaptic bursts could be evoked, but intrinsic bursting became rare. These changes persisted for at least 1 month. We postulate that this transition from intrinsic to synaptic hyperexcitability may be important in the development of TLE.