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The Journal of Neuroscience, October 14, 2009, 29(41):12896-12908; doi:10.1523/JNEUROSCI.6160-08.2009

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Cellular/Molecular
Input-Specific Intrasynaptic Arrangements of Ionotropic Glutamate Receptors and Their Impact on Postsynaptic Responses

Etsuko Tarusawa,1,2 Ko Matsui,1,2,4 Timotheus Budisantoso,1,2 Elek Molnár,5 Masahiko Watanabe,6 Minoru Matsui,7 Yugo Fukazawa,1,2 and Ryuichi Shigemoto1,2,3

1Division of Cerebral Structure, National Institute for Physiological Sciences, and 2Department of Physiological Sciences, Graduate University for Advanced Studies (SOKENDAI), Okazaki 444-8787, Japan, 3SORST and 4PRESTO, Japan Science and Technology Agency, Kawaguchi 333-0012, Japan, 5Medical Research Council Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, School of Medical Sciences, Bristol BS8 1TD, United Kingdom, 6Department of Anatomy, Hokkaido University, School of Medicine, Sapporo 060-8638, Japan, and 7Faculty of Pharmacy, Chiba Institute of Science, Choshi 288-0025, Japan

Correspondence should be addressed to either Yugo Fukazawa or Ko Matsui (Simulation & Electrophysiology), Division of Cerebral Structure, National Institute for Physiological Sciences, Okazaki 444-8787, Japan, Email: yugo{at}nips.ac.jp or Email: matsui{at}nips.ac.jp

To examine the intrasynaptic arrangement of postsynaptic receptors in relation to the functional role of the synapse, we quantitatively analyzed the two-dimensional distribution of AMPA and NMDA receptors (AMPARs and NMDARs, respectively) using SDS-digested freeze-fracture replica labeling (SDS-FRL) and assessed the implication of distribution differences on the postsynaptic responses by simulation. In the dorsal lateral geniculate nucleus, corticogeniculate (CG) synapses were twice as large as retinogeniculate (RG) synapses but expressed similar numbers of AMPARs. Two-dimensional views of replicas revealed that AMPARs form microclusters in both synapses to a similar extent, resulting in larger AMPAR-lacking areas in the CG synapses. Despite the broad difference in the AMPAR distribution within a synapse, our simulations based on the actual receptor distributions suggested that the AMPAR quantal response at individual RG synapses is only slightly larger in amplitude, less variable, and faster in kinetics than that at CG synapses having a similar number of the receptors. NMDARs at the CG synapses were expressed twice as many as those in the RG synapses. Electrophysiological recordings confirmed a larger contribution of NMDAR relative to AMPAR-mediated responses in CG synapses. We conclude that synapse size and the density and distribution of receptors have minor influences on quantal responses and that the number of receptors acts as a predominant postsynaptic determinant of the synaptic strength mediated by both the AMPARs and NMDARs.


Received Dec. 26, 2008; revised July 24, 2009; accepted Aug. 30, 2009.

Correspondence should be addressed to either Yugo Fukazawa or Ko Matsui (Simulation & Electrophysiology), Division of Cerebral Structure, National Institute for Physiological Sciences, Okazaki 444-8787, Japan, Email: yugo{at}nips.ac.jp or Email: matsui{at}nips.ac.jp






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Copyright 2009 by Society for Neuroscience ONLINE ISSN: 1529-2401
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