AUTHOR=Zhang Hongyu , Bramham Clive R. 

TITLE=Bidirectional Dysregulation of AMPA Receptor-Mediated Synaptic Transmission and Plasticity in Brain Disorders

JOURNAL=Frontiers in Synaptic Neuroscience

VOLUME=Volume 12 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/synaptic-neuroscience/articles/10.3389/fnsyn.2020.00026

DOI=10.3389/fnsyn.2020.00026

ISSN=1663-3563

ABSTRACT=AMPA receptors (AMPARs) are glutamate-gated ion channels that mediate the majority of fast excitatory synaptic transmission throughout the brain. Changes in the properties and postsynaptic abundance of AMPARs are pivotal mechanisms in synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD) of synaptic transmission. A wide range of neurodegenerative, neurodevelopmental and neuropsychiatric disorders, despite their extremely diverse etiology, pathogenesis and symptoms, exhibit brain region-specific and AMPAR subunit-specific aberrations in synaptic transmission or plasticity. Reversal of changes in AMPAR-mediated transmission or synaptic plasticity by targeting AMPAR subunits or trafficking ameliorates drug-seeking behavior, chronic pain, epileptic seizure, or cognitive deficits. This indicates that dysregulation of AMPAR-mediated synaptic transmission or plasticity may contribute to the expression of many brain disorders and therefore serve as a therapeutic target. Here, we provide a synopsis of AMPAR dysregulation in animal models of brain disorders and review the preclinical evidence on the therapeutic targeting of AMPARs.