Febrile Seizures Cause a Rapid Depletion of Calcium-Permeable AMPA Receptors at the Synapses of Principal Neurons in the Entorhinal Cortex and Hippocampus of the Rat

Abstract

Febrile seizures (FSs) are a relatively common early-life condition that can cause CNS developmental disorders, but the specific mechanisms of action of FS are poorly understood. In this work, we used hyperthermia-induced FS in 10-day-old rats. We demonstrated that the efficiency of glutamatergic synaptic transmission decreased rapidly after FS by recording local field potentials. This effect was transient, and after two days there were no differences between control and post-FS groups. During early ontogeny, the proportion of calcium-permeable (CP)-AMPA receptors in the synapses of the principal cortical and hippocampal neurons is high. Therefore, rapid internalization of CP-AMPA receptors may be one of the mechanisms underlying this phenomenon. Using the whole-cell patch-clamp method and the selective CP-AMPA receptor blocker IEM-1460, we tested whether the proportion of CP-AMPA receptors changed. We have demonstrated that FS rapidly reduces synaptic CP-AMPA receptors in both the hippocampus and the entorhinal cortex. This process was accompanied by a sharp decrease in the calcium permeability of the membrane of principal neurons, which we revealed in experiments with kainate-induced cobalt uptake. Our experiments show that FSs cause rapid changes in the function of the glutamatergic system, which may have compensatory effects that prevent excessive excitotoxicity and neuronal death.

Alterations in Rat Hippocampal Glutamatergic System Properties after Prolonged Febrile Seizures

“…Conversely, febrile seizures cause a rapid decrease in the proportion of calcium-permeable AMPA receptors in the synapses of pyramidal neurons [49].…”

Light-Sensitive Open Channel Block of Ionotropic Glutamate Receptors by Quaternary Ammonium Azobenzene Derivatives

“…The effects of the drugs were tested on the hippocampal pyramidal neurons of the CA1 area, expressing the NMDA and AMPA calcium-impermeable receptors [52][53][54][55], and on the giant cholinergic interneurons of the striatum, expressing calcium-permeable AMPA receptors [56]. The expression of calcium-permeable AMPA receptors in hippocampal pyramidal cells of the CA1 region cannot be entirely excluded, especially regarding the age of the animals used in this study [56][57][58]. We regularly used IEM-1925, a voltagedependent and use-dependent channel blocker of calcium-permeable AMPA receptors, as a reference compound for the pharmacological identification of a receptor subpopulation (Tikhonov et al, 2000) [37].…”