Linking nanoscale dynamics of AMPA receptor organization to plasticity of excitatory synapses and learning

Daniel Choquet
J. Neurosci.. 2018-10-31; 38(44): 9318-9329
DOI: 10.1523/JNEUROSCI.2119-18.2018

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The spatiotemporal organization of neurotransmitter receptors in the postsynaptic
membrane is a fundamental determinant of synaptic transmission and thus of
information processing by the brain. The ionotropic AMPA subtype of glutamate
receptors (AMPARs) mediate fast excitatory synaptic transmission in the CNS. The
number of AMPARs located en face presynaptic glutamate release sites sets the
efficacy of synaptic transmission. Understanding how this number is set and
regulated has been the topic of intense research in the last two decades. We
showed that AMPARs are not stable in the synapse as initially thought. They
continuously enter and exit the postsynaptic density by lateral diffusion, and
they exchange between the neuronal surface and intracellular compartments by
endocytosis and exocytosis at extrasynaptic sites. Regulation of these various
trafficking pathways has emerged as a key mechanism for activity-dependent
plasticity of synaptic transmission, a process important for learning and memory.
I here present my view of these findings. In particular, the advent of
super-resolution microscopy and single-molecule tracking has helped to uncover
the intricacy of AMPARs’ dynamic organization at the nanoscale. In addition,
AMPAR surface diffusion is highly regulated by a variety of factors, including
neuronal activity, stress hormones, and neurodegeneration, suggesting that AMPAR
diffusion-trapping may play a central role in synapse function. Using innovative
tools to understand further the link between receptor dynamics and synapse
plasticity is now unveiling new molecular mechanisms of learning. Modifying AMPAR
dynamics may emerge as a new target to correct synapse dysfunction in the
diseased brain.


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