Abstract
In the mammalian central nervous system, excitatory glutamatergic synapses harness neurotransmission that is mediated by ion flow through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). AMPARs, which are enriched in the postsynaptic membrane on dendritic spines, are highly dynamic, and shuttle in and out of synapses in an activity-dependent manner. Changes in their number, subunit composition, phosphorylation state, and accessory proteins can all regulate AMPARs and thus modify synaptic strength and support cellular forms of learning. Furthermore, dysregulation of AMPAR plasticity has been implicated in various pathological states and has important consequences for mental health. Here we focus on the mechanisms that control AMPAR plasticity, drawing particularly from the extensive studies on hippocampal synapses, and highlight recent advances in the field along with considerations for future directions.
Highlights
The birth of modern neuroscience arguably started with the seminal work of Cajal (1852–1934, Doyle, 1939) who identified neurons as individual units embedded within the vastly complex network of brain tissue
Studies at the neuromuscular junction, an experimental preparation that was more accessible than the brain, demonstrated that postsynaptic receptors were largely stable and were generally unresponsive to changes in activity level (Fambrough and Hartzell, 1972; Sanes and Lichtman, 1999). Whether this applied to the central nervous system was begun to be answered in the 1970s and 80s, when Bliss and Lømo, working in rabbit hippocampus, first demonstrated that a stimulus could cause an increase in synaptic strength that was long lasting, termed long-term potentiation (LTP: Bliss and Lømo, 1973)
After a brief introduction to the discovery and history of AMPARs, this review focuses on their role in postsynaptic plasticity in the hippocampus and the recent advances over the last few years
Summary
Reviewed by: Lisa Mapelli, University of Pavia, Italy Davide Pozzi, Humanitas Research Hospital, Italy. AMPARs, which are enriched in the postsynaptic membrane on dendritic spines, are highly dynamic, and shuttle in and out of synapses in an activity-dependent manner. Changes in their number, subunit composition, phosphorylation state, and accessory proteins can all regulate AMPARs and modify synaptic strength and support cellular forms of learning. Dysregulation of AMPAR plasticity has been implicated in various pathological states and has important consequences for mental health. We focus on the mechanisms that control AMPAR plasticity, drawing from the extensive studies on hippocampal synapses, and highlight recent advances in the field along with considerations for future directions
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