Super-resolution imaging reveals that AMPA receptors inside synapses are dynamically organized in nanodomains regulated by PSD95.
Journal of Neuroscience. 2013-08-07; 33(32): 13204-13224
DOI: 10.1523/jneurosci.2381-12.2013
Read on PubMed
1. J Neurosci. 2013 Aug 7;33(32):13204-24. doi: 10.1523/JNEUROSCI.2381-12.2013.
Super-resolution imaging reveals that AMPA receptors inside synapses are
dynamically organized in nanodomains regulated by PSD95.
Nair D(1), Hosy E, Petersen JD, Constals A, Giannone G, Choquet D, Sibarita JB.
Author information:
(1)University of Bordeaux, Interdisciplinary Institute for Neuroscience, and
Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5297,
F-33000 Bordeaux, France.
Comment in
J Neurosci. 2013 Dec 4;33(49):19048-50.
The spatiotemporal organization of neurotransmitter receptors in postsynaptic
membranes is a fundamental determinant of synaptic transmission and information
processing by the brain. Using four independent super-resolution light imaging
methods and EM of genetically tagged and endogenous receptors, we show that, in
rat hippocampal neurons, AMPARs are often highly concentrated inside synapses
into a few clusters of ∼70 nm that contain ∼20 receptors. AMPARs are stabilized
reversibly in these nanodomains and diffuse freely outside them. Nanodomains are
dynamic in their shape and position within synapses and can form or disappear
within minutes, although they are mostly stable for up to 1 h. AMPAR nanodomains
are often, but not systematically, colocalized with clusters of the scaffold
protein PSD95, which are generally of larger size than AMPAR nanoclusters. PSD95
expression level regulates AMPAR nanodomain size and compactness in parallel to
miniature EPSC amplitude. Monte Carlo simulations further indicate the impact of
AMPAR concentration in clusters on the efficacy of synaptic transmission. The
observation that AMPARs are highly concentrated in nanodomains, instead of
diffusively distributed in the PSD as generally thought, has important
consequences on our understanding of excitatory neurotransmission. Furthermore,
our results indicate that glutamatergic synaptic transmission is controlled by
the nanometer-scale regulation of the size of these highly concentrated
nanodomains.
DOI: 10.1523/JNEUROSCI.2381-12.2013
PMID: 23926273 [Indexed for MEDLINE]