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AMPA receptors and synaptic plasticity: a chemist's perspective

Nature Chemical Biology volume 6, pages 89–97 (2010)Cite this article

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Abstract

The ability of the mammalian brain to undergo experience-based adaptations is among its most important and fascinating properties. Such plasticity is reflected in the capacity of neuronal activity to continuously modify the neural circuitry that underlies thought, feeling and behavior. The locus of this plasticity occurs at the level of synapses, the specialized junctions where one neuron receives chemical signals from another. Synaptic connections become stronger or weaker in response to specific patterns of activity. This activity drives regulated changes in the neurotransmitter released by presynaptic neurons and in the receptors localized on postsynaptic neurons. Detailed studies of these receptors have advanced our understanding of synaptic plasticity. However, many key questions remain unresolved, and over the past decade innovative chemical approaches have emerged to tackle them. Here we review these chemical tools and their application to unraveling the molecular basis of synaptic plasticity.

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Figure 1: LTP and LTD.
Figure 2: AMPA receptor structure and function.
Figure 3: Trafficking of AMPA receptors.
Figure 4: Structures of the chemical genetic and chemical tools discussed in the text.

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Acknowledgements

We thank B. Shoichet and K. Shokat for their critical review of the manuscript. We apologize to those whose work we could not cite because of space limitations. J.J.F. is supported by grants from the Wheeler Center and the Sandler Foundation. Work in the lab of P.M.E. is supported by the US National Institutes of Health, the McKnight Foundation and the Sandler Foundation.

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  1. Department of Pharmaceutical Chemistry and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California, USA

    James J Fleming & Pamela M England

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Fleming, J., England, P. AMPA receptors and synaptic plasticity: a chemist's perspective. Nat Chem Biol 6, 89–97 (2010). https://doi.org/10.1038/nchembio.298

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