Expression of a Putative Vesicular Acetylcholine Transporter Facilitates Quantal Transmitter Packaging

Song, Hong; Guo, Ming; Fon, Edward A.; Bellocchio, Elizabeth E.; Edwards, Robert H.; Poo, Mu Ming

doi:10.1016/s0896-6273(00)80320-7

Cited by 164 publications

(133 citation statements)

References 39 publications

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“…The set point of synaptic vesicle glutamate and GABA storage might therefore be controlled by the number of functional transporters and the cytoplasmic transmitter concentration (Wilson et al, 2005) similarly to that described for the vesicular acetylcholine transporter after heterologous gene expression Erickson, 1996, 1997), supporting a steady-state equilibrium model of vesicle transmitter packet size (Williams, 1997). The rate of vesicular transmitter uptake Song et al, 1997) and the size of synaptic vesicles have also been considered to be determinants of quantal size (Bruns et al, 2000;Colliver et al, 2000;Pothos et al, 2000;Sulzer and Pothos, 2000;Karunanithi et al, 2002;Van der Kloot et al, 2002;Gong et al, 2003). VGLUT1 overexpression at excitatory synapses of Drosophila results in an increase in vesicle volume, which is accompanied by an increase in quantal size of glutamate measured postsynaptically (Daniels et al, 2004).…”

Section: Scaling Of Vesicular Glutamate and Gaba Transporter Expressionmentioning

confidence: 66%

Homeostatic Scaling of Vesicular Glutamate and GABA Transporter Expression in Rat Neocortical Circuits

Gois

Schäfer²,

Defamie³

et al. 2005

J. Neurosci.

174

183

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Homeostatic control of pyramidal neuron firing rate involves a functional balance of feedforward excitation and feedback inhibition in neocortical circuits. Here, we reveal a dynamic scaling in vesicular excitatory (vesicular glutamate transporters VGLUT1 and VGLUT2) and inhibitory (vesicular inhibitory amino acid transporter VIAAT) transporter mRNA and synaptic protein expression in rat neocortical neuronal cultures, using a well established in vitro protocol to induce homeostatic plasticity. During the second and third week of synaptic differentiation, the predominant vesicular transporters expressed in neocortical neurons, VGLUT1 and VIAAT, are both dramatically upregulated. In mature cultures, VGLUT1 and VIAAT exhibit bidirectional and opposite regulation by prolonged activity changes. Endogenous coregulation during development and homeostatic scaling of the expression of the transporters in functionally differentiated cultures may serve to control vesicular glutamate and GABA filling and adjust functional presynaptic excitatory/inhibitory balance. Unexpectedly, hyperexcitation in differentiated cultures triggers a striking increase in VGLUT2 mRNA and synaptic protein, whereas decreased excitation reduces levels. VGLUT2 mRNA and protein are expressed in subsets of VGLUT1-encoded neocortical neurons that we identify in primary cultures and in neocortex in situ and in vivo. After prolonged hyperexcitation, downregulation of VGLUT1/ synaptophysin intensity ratios at most synapses is observed, whereas a subset of VGLUT1-containing boutons selectively increase the expression of VGLUT2. Bidirectional and opposite regulation of VGLUT1 and VGLUT2 by activity may serve as positive or negative feedback regulators for cortical synaptic transmission. Intracortical VGLUT1/VGLUT2 coexpressing neurons have the capacity to independently modulate the level of expression of either transporter at discrete synapses and therefore may serve as a plastic interface between subcortical thalamic input (VGLUT2) and cortical output (VGLUT1) neurons.

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Section: Scaling Of Vesicular Glutamate and Gaba Transporter Expressionmentioning

confidence: 66%

Homeostatic Scaling of Vesicular Glutamate and GABA Transporter Expression in Rat Neocortical Circuits

Gois

Schäfer²,

Defamie³

et al. 2005

J. Neurosci.

174

183

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“…At the frog neuromuscular junction, the vesicular acetylcholine transporter expression level seems to be the limiting factor for cholinergic quantal size (38), and the same appears to be true for vesicular packaging of monoamines, which is enhanced by vesicular monoamine transporter 2 overexpression in PC12 cells and ventral midbrain neurons, whereas total monoamine stores are reduced in the brains of vesicular monoamine transporter 2 ϩ͞Ϫ mice (39)(40)(41). In vivo, demands made on the vesicular filling rate are likely to differ between vesicular acetylcholine transporter, vesicular monoamine transporter, and VGLUT, and they might be particularly high for VGLUT.…”

Section: Discussionmentioning

confidence: 99%

An essential role for vesicular glutamate transporter 1 (VGLUT1) in postnatal development and control of quantal size

Wojcik

Rhee

Herzog

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

447

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Quantal neurotransmitter release at excitatory synapses depends on glutamate import into synaptic vesicles by vesicular glutamate transporters (VGLUTs). Of the three known transporters, VGLUT1 and VGLUT2 are expressed prominently in the adult brain, but during the first two weeks of postnatal development, VGLUT2 expression predominates. Targeted deletion of VGLUT1 in mice causes lethality in the third postnatal week. Glutamatergic neurotransmission is drastically reduced in neurons from VGLUT1-deficient mice, with a specific reduction in quantal size. The remaining activity correlates with the expression of VGLUT2. This reduction in glutamatergic neurotransmission can be rescued and enhanced with overexpression of VGLUT1. These results show that the expression level of VGLUTs determines the amount of glutamate that is loaded into vesicles and released and thereby regulates the efficacy of neurotransmission.

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“…At calyces, glutamate dialysis increases the mEPSC (Ishikawa et al, 2002;Yamashita et al, 2003), suggesting that [Glu] v can be upregulated. At other nerve terminals, overexpression or knock-out of vesicular transporters increases or decreases quantal size (Song et al, 1997;Wojcik et al, 2004;Wilson et al, 2005). The change in quantal size is presumably caused by changes in the vesicular transmitter concentration, although vesicle volume was not measured to ascertain the conclusion.…”

Section: Discussionmentioning

confidence: 99%

“…First, overexpression of vesicular transporter for transmitters like acetylcholine and glutamate increases the quantal size (Song et al, 1997;Wojcik et al, 2004;Wilson et al, 2005). Second, increasing the cytosolic glutamate concentration elevates the vesicular glutamate concentration at calyx-type synapses (Ishikawa et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

The Origin of Quantal Size Variation: Vesicular Glutamate Concentration Plays a Significant Role

Xue

Mohan

et al. 2007

J. Neurosci.

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Fusion of a single vesicle induces a quantal response, which is critical in determining synaptic strength. Quantal size varies at most synapses. Its underlying mechanisms are not well understood. Here, we examined five sources of variation: vesicular glutamate concentration ([Glu] v ), vesicle volume, ultrafast fusion pore closure, the postsynaptic receptor, and the location between release and the postsynaptic receptor cluster at glutamatergic, calyx of Held synapses. By averaging 2.66 million fusion events from 459 synapses, we resolved the capacitance jump evoked by single vesicle fusion. This capacitance jump, an indicator of vesicle volume, was independent of the amplitude of the miniature EPSC (mEPSC) recorded simultaneously at the same synapses. Thus, vesicle volume is not the main source of mEPSC variation. The capacitance jump was not followed by submillisecond endocytosis, excluding ultrafast endocytosis as a source of variation. Larger mEPSCs were increased to a lesser extent by presynaptic glutamate dialysis, and reduced to a lesser extent by ␥-DGG (␥-D-glutamylglycine), a competitive AMPA receptor blocker, suggesting that a higher glutamate concentration in the synaptic cleft contributes to the large size of mEPSCs. Larger mEPSCs were not accompanied by briefer rise times, inconsistent with the prediction by, and thus arguing against, the scenario that larger mEPSCs are caused by a shorter distance between the release site and the postsynaptic receptor cluster. In summary, the different amplitudes of mEPSCs were mainly attributable to release of vesicles having similar volumes, but different glutamate amounts, suggesting that [Glu] v is a main source of quantal size variation.

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Expression of a Putative Vesicular Acetylcholine Transporter Facilitates Quantal Transmitter Packaging

Cited by 164 publications

References 39 publications

Homeostatic Scaling of Vesicular Glutamate and GABA Transporter Expression in Rat Neocortical Circuits

Homeostatic Scaling of Vesicular Glutamate and GABA Transporter Expression in Rat Neocortical Circuits

An essential role for vesicular glutamate transporter 1 (VGLUT1) in postnatal development and control of quantal size

The Origin of Quantal Size Variation: Vesicular Glutamate Concentration Plays a Significant Role

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