The Reactive Plasticity of Hippocampal Ionotropic Glutamate Receptors in Animal Epilepsies

Abstract

Ionotropic glutamate receptors (iGluRs) mediate the synaptic and metabolic actions of glutamate. These iGluRs are classified within the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type, kainate-type, and N-methyl-d-aspartate (NMDA)-type functional receptor families. The iGluR assemblies are regulated by transcription, alternative splicing, and cytoplasmic post-translational modifications. The iGluR subunit proteins are transported from the endoplasmic reticulum, inserted into the synaptic membranes, and anchored at their action site by different scaffolding and interacting proteins. The functional properties of iGluRs depend on their subunit composition, the amino acid sequence of the protein domains, and the scaffolding proteins in the synaptic membranes. The iGluRs are removed from the membranes by enzymatic action and endocytosis. Hippocampal iGluRs are rearranged through the upregulation and downregulation of the subunits following deafferentation and epileptic seizures. The rearrangement of iGluRs and the alteration of their subunit composition transform neurons into “pathological” cells, determining the further plasticity or pathology of the hippocampal formation. In the present review, we summarize the expression of AMPA, kainate, and NMDA receptor subunits following deafferentation, repeated mild seizures, and status epilepticus. We compare our results to literature descriptions, and draw conclusions as to the reactive plasticity of iGluRs in the hippocampus.

Stress-Associated Molecular and Cellular Hippocampal Mechanisms Common for Epilepsy and Comorbid Depressive Disorders

“…It induces neurodegenerative changes and loss of hippocampal neurons. Aberrant signaling BIOCHEMISTRY (Moscow) affects both ionotropic [102,103] and metabotropic glu tamate receptors [104] and induces the excitotoxicity and oxidative stress, which also contribute to the comorbidity of TLE and psychiatric diseases [93,105]. It is important to note that the functioning of glutamatergic synapses carrying mineralocorticoid receptors and GRs on the membrane and in the cytoplasm is regulated by GCs via multiple pathways (see review [51]).…”

The emerging role of kainate receptor functional dysregulation in pain

“… 31 , 32 In addition, they can facilitate macromolecule and molecular aggregate anchoring, thereby influencing long-term synaptic plasticity in the hippocampus, cortex, and amygdalas. 33 , 34 …”

Animal models for epileptic foci localization, seizure detection, and prediction by electrical impedance tomography

“…4‐aminopyridine is an organic compound that functions as a K + channel blocker, and it is commonly used as a pesticide, medicine, and dye intermediate. Intrahippocampal administration of a high concentration (35–70 mM) of 4‐aminopyridine induces seizures and severe neurodegeneration in the hippocampal CA1, CA3, and CA4 subfields due to the increased release of glutamate from excitatory neurons (Mihaly, 2019).…”