Genetic manipulations of AMPA glutamate receptors in hippocampal synaptic plasticity. 2021

Radu Gugustea, and Zhengping Jia
The Hospital for Sick Children, Neurosciences and Mental Health Program, Peter Gilgan Centre for Research and Learning, Toronto, ON, Canada; Department of Physiology, Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are the principal mediators of fast excitatory synaptic transmission and they are required for various forms of synaptic plasticity, including long-term potentiation (LTP) and depression (LTD), which are key mechanisms of learning and memory. AMPARs are tetrameric complexes assembled from four subunits (GluA1-4), however, the lack of subunit-specific pharmacological tools has made the assessment of individual subunits difficult. The application of genetic techniques, particularly gene targeting, allows for precise manipulation and dissection of each subunit in the regulation of neuronal function and behaviour. In this review, we summarize studies using various mouse models with genetically altered AMPARs and focus on their roles in basal synaptic transmission, LTP, and LTD at the hippocampal CA1 synapse. These studies provide strong evidence that there are multiple forms of LTP and LTD at this synapse which can be induced by various induction protocols, and they are differentially regulated by different AMPAR subunits and domains. We conclude that it is necessary to delineate the mechanism of each of these forms of plasticity and their contribution to memory and brain disorders.

UI MeSH Term Description Entries
D007858 Learning Relatively permanent change in behavior that is the result of past experience or practice. The concept includes the acquisition of knowledge. Phenomenography
D008957 Models, Genetic Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment. Genetic Models,Genetic Model,Model, Genetic
D009473 Neuronal Plasticity The capacity of the NERVOUS SYSTEM to change its reactivity as the result of successive activations. Brain Plasticity,Plasticity, Neuronal,Axon Pruning,Axonal Pruning,Dendrite Arborization,Dendrite Pruning,Dendritic Arborization,Dendritic Pruning,Dendritic Remodeling,Neural Plasticity,Neurite Pruning,Neuronal Arborization,Neuronal Network Remodeling,Neuronal Pruning,Neuronal Remodeling,Neuroplasticity,Synaptic Plasticity,Synaptic Pruning,Arborization, Dendrite,Arborization, Dendritic,Arborization, Neuronal,Arborizations, Dendrite,Arborizations, Dendritic,Arborizations, Neuronal,Axon Prunings,Axonal Prunings,Brain Plasticities,Dendrite Arborizations,Dendrite Prunings,Dendritic Arborizations,Dendritic Prunings,Dendritic Remodelings,Network Remodeling, Neuronal,Network Remodelings, Neuronal,Neural Plasticities,Neurite Prunings,Neuronal Arborizations,Neuronal Network Remodelings,Neuronal Plasticities,Neuronal Prunings,Neuronal Remodelings,Neuroplasticities,Plasticities, Brain,Plasticities, Neural,Plasticities, Neuronal,Plasticities, Synaptic,Plasticity, Brain,Plasticity, Neural,Plasticity, Synaptic,Pruning, Axon,Pruning, Axonal,Pruning, Dendrite,Pruning, Dendritic,Pruning, Neurite,Pruning, Neuronal,Pruning, Synaptic,Prunings, Axon,Prunings, Axonal,Prunings, Dendrite,Prunings, Dendritic,Prunings, Neurite,Prunings, Neuronal,Prunings, Synaptic,Remodeling, Dendritic,Remodeling, Neuronal,Remodeling, Neuronal Network,Remodelings, Dendritic,Remodelings, Neuronal,Remodelings, Neuronal Network,Synaptic Plasticities,Synaptic Prunings
D006624 Hippocampus A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation. Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D017470 Receptors, Glutamate Cell-surface proteins that bind glutamate and trigger changes which influence the behavior of cells. Glutamate receptors include ionotropic receptors (AMPA, kainate, and N-methyl-D-aspartate receptors), which directly control ion channels, and metabotropic receptors which act through second messenger systems. Glutamate receptors are the most common mediators of fast excitatory synaptic transmission in the central nervous system. They have also been implicated in the mechanisms of memory and of many diseases. Excitatory Amino Acid Receptors,Glutamate Receptors,Receptors, Excitatory Amino Acid,Excitatory Amino Acid Receptor,Glutamate Receptor,Receptor, Glutamate
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D018091 Receptors, AMPA A class of ionotropic glutamate receptors characterized by their affinity for the agonist AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid). AMPA Receptors,Quisqualate Receptors,AMPA Receptor,Quisqualate Receptor,Receptor, AMPA,Receptor, Quisqualate,Receptors, Quisqualate
D018350 alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid An IBOTENIC ACID homolog and glutamate agonist. The compound is the defining agonist for the AMPA subtype of glutamate receptors (RECEPTORS, AMPA). It has been used as a radionuclide imaging agent but is more commonly used as an experimental tool in cell biological studies. AMPA,AMPA, (+-)-Isomer,AMPA, (R)-Isomer,AMPA, (R)-Isomer, Monohydrobromide,AMPA, (S)-Isomer,AMPA, (S)-Isomer, Monohydrobromide,alpha Amino 3 hydroxy 5 methyl 4 isoxazolepropionic Acid
D018390 Gene Targeting The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. Gene Targetings,Targeting, Gene,Targetings, Gene

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