4.7 Article

Linking Nanoscale Dynamics of AMPA Receptor Organization to Plasticity of Excitatory Synapses and Learning

期刊

JOURNAL OF NEUROSCIENCE
卷 38, 期 44, 页码 9318-9329

出版社

SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2119-18.2018

关键词

Synaptic plasticity; AMPA receptors; receptor trafficking; super resolution imaging; Long Term Potentiation; neurodegen-erative diseases

资金

  1. Ministere de l'Enseignement Superieur et de la Recherche
  2. Centre National de la Recherche Scientifique
  3. ERC Grant ADOS
  4. Conseil Regional de Nouvelle Aquitaine

向作者/读者索取更多资源

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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