Input-specific intrasynaptic arrangements of ionotropic glutamate receptors and their impact on postsynaptic responses.
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.
Tarusawa
Etsuko
E
Division of Cerebral Structure, National Institute for Physiological Sciences, Department of Physiological Sciences, Graduate University for Advanced Studies (SOKENDAI), Okazaki 444-8787, Japan.
Matsui
Ko
K
Budisantoso
Timotheus
T
Molnár
Elek
E
Watanabe
Masahiko
M
Matsui
Minoru
M
Fukazawa
Yugo
Y
Shigemoto
Ryuichi
R
D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005614:Freeze Fracturing / Q000379:methods; D005829:Geniculate Bodies / Q000166:cytology; D018698:Glutamic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron / Q000379:methods; D009434:Neural Pathways / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D020318:Rats, Long-Evans; D043585:Receptor, Muscarinic M2 / Q000172:deficiency; D018091:Receptors, AMPA / Q000145:classification / Q000378:metabolism* / Q000648:ultrastructure; D016194:Receptors, N-Methyl-D-Aspartate / Q000145:classification / Q000378:metabolism* / Q000648:ultrastructure; D012160:Retina / Q000166:cytology / Q000502:physiology; D018709:Statistics, Nonparametric; D013569:Synapses / Q000145:classification / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism
D043585:Receptor, Muscarinic M2; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D050598:Vesicular Glutamate Transport Protein 1; D050599:Vesicular Glutamate Transport Protein 2; D018698:Glutamic Acid