Abstracts

Rationale: Alterations in neurotransmitter receptor function have been implicated as a disease mechanism in temporal lobe epilepsy (TLE), and may also contribute to epileptogenesis during the latent period of TLE. In this study we examined both glutamate receptor function and excitatory synaptic responses in hippocampal dentate granule cells (DGCs) during the latent period of TLE.Methods: The rodent pilocarpine TLE model was used in the current study. Two loci of receptor populations were separated using a combination of acutely isolated neurons and brain slice recording. Due to loss of dendrites during the isolation procedure, glutamate receptor responses recorded in acutely isolated neurons are derived from predominantly somatic receptors, while recordings of excitatory synaptic responses in brain slice studies represent responses of subsynaptic receptors in the dendrites of DGCs. One week post Status Epilepticus, the function of pharmacologically isolated AMPA and NMDA receptors in acutely dissociated DGCs were examined using whole cell patch clamp techniques, and synaptic responses were recorded from DGCs in hippocampal brain slices using visualized slice patch techniques. Results: One-week post Status Epilepticus, capacitance-normalized current density and total charge transfer for both AMPA and NMDA receptor mediated responses were significantly reduced in acutely isolated DGCs. In contrast, there was no significant change in sEPSC amplitude at subsynaptic glutamate receptors. In addition, there was an increase in sEPSC decay time constant resulting in an increase in total charge transfer.Conclusions: The differential sensitivity of receptor responses in acutely isolated neurons and synaptic responses in slice recordings suggest distinct regulation of glutamate receptor function in cell soma and dendritic spines in DGCs during the latent period of TLE. A possible explanation could be that glutamate receptor transcriptional/translational machinery localized under dendritic spines is regulated autonomously, while somatic expression of glutamate receptors is controlled by nuclear transcription and translation, which is repressed during the latent period. Since previous laboratory data have demonstrated significant reduction in inhibition in DGCs during the latent period, the maintained function of glutamate receptors at subsynaptic sites may then increase the excitability of DGCs and contribute to epileptogenesis.