Changes in excitatory and inhibitory receptor expression and network activity during induction and establishment of epilepsy in the rat Reduced Intensity Status Epilepticus (RISE) model. (1st November 2019)

• Record Type: Journal Article
• Authors: Needs, Hope I.; Henley, Benjamin S.; Cavallo, Damiana; Gurung, Sonam; Modebadze, Tamara; Woodhall, Gavin; Henley, Jeremy M.
• Is Part Of: Neuropharmacology. Volume 158(2019)
• Publication Date: 2019-11-01
• Subjects: Temporal lobe epilepsy -- AMPA receptors -- Synapse -- Reduced intensity status epilepticus (RISE) model; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2019.107728
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: The RISE model is an effective system to study the underlying molecular and cellular mechanisms involved in the initiation and maintenance of epilepsy in vivo . Here we profiled the expression of excitatory and inhibitory neurotransmitter receptor subunits and synaptic scaffolding proteins in the hippocampus and temporal lobe and compared these changes with alterations in network activity at specific timepoints during epileptogenesis. Significant changes occurred in all of the ionotropic glutamate receptor subunits tested during epilepsy induction and progression and the profile of these changes differed between the hippocampus and temporal lobe. Notably, AMPAR subunits were dramatically decreased during the latent phase of epilepsy induction, matched by a profound decrease in the network response to kainate application in the hippocampus. Moreover, decreases in the GABAA β3 subunit are consistent with a loss of inhibitory input contributing to the perturbation of excitatory/inhibitory balance and seizure generation. These data highlight the synaptic reorganisation that mediates the relative hypoexcitability prior to the manifestation of seizures and subsequent hyperexcitability when spontaneous seizures develop. These patterns of changes give new insight into the mechanisms underpinning epilepsy and provide a platform for future investigations targeting particular receptor subunits to reduce or prevent seizures. Highlights: Changes in synaptic protein levels provide insight into synaptic reorganisation in epilepsy. In the RISE model changes in GluR subunits occur at different stages of epileptogenesis. Changes appear to occur independently of changes in synapse number. GluR profiles are directly linked to changes in network excitability. Targeting GluR subunits could provide a new strategy to reduce seizures.