Nonsaturation of AMPA and NMDA receptors at hippocampal synapses

McAllister, A. Kimberley; Stevens, Charles F.

doi:10.1073/pnas.100126497

Cited by 196 publications

(179 citation statements)

References 36 publications

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“…This analysis predicted the number of AMPA receptors to be 46 to 147 (82 ± 31; mean ± s.d., n = 8) and the amplitude of single-channel currents to be 0.4 to 0.8 pA (0.6 ± 0.1). As a corollary, our data suggest that the postsynaptic AMPA receptors in the mushroom spines are not saturated by the glutamate released from a single synaptic vesicle 23,33 , because the opening probability of the AMPA receptors was estimated as 0.27, given that the largest mEPSC was ~19 pA (n = 222) in our experiments, and that such mEPSC likely occurred in the mushroom spines with largest number of AMPA receptors (N = 147, i = 0.48 pA). …”

mentioning

confidence: 70%

“…2-6). Cultured neurons, stained with 10 μM FM1-43 and 40 mM KCl for 1 min and then washed for more than 5 min 33 , were imaged before the wholecell clamp experiments with a cooled charged-coupled devise camera (TILL Photonics, Munich, Germany; Fig. 2g).…”

Section: Two-photon Excitation Of a Caged-glutamate Compoundmentioning

confidence: 99%

“…2g and h). Thus, our functional mapping approach was able to detect the clustering of AMPA receptors in the postsynaptic membrane 23,32,33 . …”

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Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons

et al. 2001

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Dendritic spines serve as preferential sites of excitatory synaptic connections and are pleomorphic. To address the structure-function relationship of the dendritic spines, we used two-photon uncaging of glutamate to allow mapping of functional glutamate receptors at the level of the single synapse. Our analyses of the spines of CA1 pyramidal neurons reveal that AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid)-type glutamate receptors are abundant (up to 150/ spine) in mushroom spines but sparsely distributed in thin spines and filopodia. The latter may be serving as the structural substrates of the silent synapses that have been proposed to play roles in development and plasticity of synaptic transmission. Our data indicate that distribution of functional AMPA receptors is tightly correlated with spine geometry and that receptor activity is independently regulated at the level of single spines.Most excitatory synaptic transmission in the mammalian central nervous system relies on glutamate as a neurotransmitter, and postsynaptic glutamate receptors are central in both the acquisition and maintenance of memory 1, 2 . Substantial biochemical evidence indicates that glutamate receptors in postsynaptic densities (PSDs) are regulated by various protein machineries that link the receptors to the cytoskeleton 3,4,5 and that control the insertion [6][7][8][9][10] and phosphorylation of the receptors 11,12 . Individual dendritic spines have been thought to act as functional compartments of glutamate receptor expression, given that they are physically and thus metabolically separated from the body of the dendrite by the narrow spine neck [13][14][15][16] . Indeed, the Hebbian principle of learning as well as most theories of neuronal networks assume that the strength of synaptic connections is subject to independent control 17 . Moreover, spine geometry has been proposed to be a key determinant of synaptic function and memory in the brain 13, 14, 18-22 . Correspondence to: Haruo Kasai. These various hypotheses have not been tested experimentally, however, because it is not possible to systematically investigate postsynaptic glutamate sensitivities at the level of the individual spine by classical electrophysiological approaches 16,23 . Also, the number of functional AMPA-sensitive glutamate receptors in individual spines has not been estimated directly. Two-photon excitation of caged-glutamate compounds may overcome these difficulties 24 as a result of the inherent three-dimensional resolution of neurotransmitter application associated with this technique. However, caged-glutamate compounds with a cross-section for two-photon absorption, a rate of photolysis, and a stability in aqueous solution sufficient for such studies have not previously been described [25][26][27] . NIH Public AccessWe developed a caged-glutamate compound and microscopic system for two-photon excitation that allowed systematic investigation of functional glutamate receptors at the level of the individual synapse. Our experiment...

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confidence: 70%

Section: Two-photon Excitation Of a Caged-glutamate Compoundmentioning

confidence: 99%

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Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons

et al. 2001

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“…It remains to be determined whether the concentration of glutamate in the photoreceptor synaptic cleft is sufficient to saturate post-synaptic glutamate receptors, as found at many (Frerking and Wilson, 1996), but not all (McAllister and Stevens, 2000), CNS synapses. If the receptors are not saturated, modulation of VGlut activity would provide a means of regulating post-synaptic response amplitude.…”

Section: Vesicular Glutamate Transportersmentioning

confidence: 99%

Synaptic transmission at retinal ribbon synapses

Heidelberger

Thoreson

Witkovsky

2005

Progress in Retinal and Eye Research

207

231

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The molecular organization of ribbon synapses in photoreceptors and ON bipolar cells is reviewed in relation to the process of neurotransmitter release. The interactions between ribbon synapseassociated proteins, synaptic vesicle fusion machinery and the voltage-gated calcium channels that gate transmitter release at ribbon synapses are discussed in relation to the process of synaptic vesicle exocytosis. We describe structural and mechanistic specializations that permit the ON bipolar cell to release transmitter at a much higher rate than the photoreceptor does, under in vivo conditions. We also consider the modulation of exocytosis at photoreceptor synapses, with an emphasis on the regulation of calcium channels.

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“…For example, it has been suggested that the glutamate released from a single vesicle may bind to between 70 and 90% of all receptor binding sites, saturating the response at individual synapses (Jonas et al, 1993;Diamond and Jahr, 1997) (but see Liu et al, 1999;McAllister and Stevens, 2000). If multiple vesicles are released simultaneously more often at individual synapses when the probability of release is high, this phenomenon might have affected the linearity of our postsynaptic measurements and caused us to underestimate the true amount of depression in the release of transmitter from the presynaptic terminals (for review, see Auger and Marty, 2000).…”

Section: Receptor Saturation and Voltage-clamp Errorsmentioning

confidence: 99%

Limit on the Role of Activity in Controlling the Release-Ready Supply of Synaptic Vesicles

Wesseling

2002

J. Neurosci.

190

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Typical fast chemical synapses in the brain weaken transiently during normal high-frequency use after expending their presynaptic supply of release-ready vesicles. Although it takes several seconds for the readily releasable pool (RRP) to refill during periods of rest, it has been suggested that the replenishment process may be orders of magnitude faster when synapses are active. Here, we measure this replenishment rate at active Schaffer collateral terminals by determining the maximum rate of release that can still be elicited when the RRP is almost completely exhausted. On average, we find that spent vesicles are replaced at a maximum unitary rate of 0.24/sec during periods of intense activity. Because the replenishment rate is similar during subsequent periods of rest, we conclude that no special mechanism accelerates the mobilization of neurotransmitter in active terminals beyond the previously reported, several-fold, residual calcium-driven modulation that persists for several seconds after bouts of intense synaptic activity. In the course of this analysis, we provide new evidence supporting the hypothesis that a simple enzymatic step limits the rate at which reserve synaptic vesicles become ready to undergo exocytosis.

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Nonsaturation of AMPA and NMDA receptors at hippocampal synapses

Cited by 196 publications

References 36 publications

Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons

Dendritic spine geometry is critical for AMPA receptor expression in hippocampal CA1 pyramidal neurons

Synaptic transmission at retinal ribbon synapses

Limit on the Role of Activity in Controlling the Release-Ready Supply of Synaptic Vesicles

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