Stochastic fluctuations of the quantal EPSC amplitude in computer simulated excitatory synapses of hippocampus

Ventriglia, Francesco; Maio, Vito Di

doi:10.1016/s0303-2647(03)00117-5

Cited by 27 publications

(28 citation statements)

References 26 publications

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“…For our diffusion process, we use Langevin equations, and, for numerical simulation, we discretize the time with a very small time step [40×10 −15 s (40 femtoseconds)], but not the space. This method, in addition to the fine geometrical representation of the synaptic space, permits a very fine description of the 3D molecular motion [3,4,[10][11][12][13]17,19,24,31,35]. In their standard form, Langevin equations are expressed as…”

Section: Diffusion Model Of Glutamatementioning

confidence: 99%

“…Considering that, vesicle concentration ranges from 60 to 210 mM [14], the size of the vesicle determines the number of glutamate molecules released during the single synaptic event [10,11,14,31,35,36,58] and, consequently, the glutamate concentration time-course in the synaptic cleft [14,31,35].…”

Section: Pre-synaptic Factorsmentioning

confidence: 99%

“…Usually, there are almost 200 vesicles in a synaptic terminal, about 10 of which are docked in different positions of AZ area [22,23]. It follows that different combinations "size/concentration/position" produce post-synaptic response variability of stochastic origin [10,19,31,35].…”

Section: Pre-synaptic Factorsmentioning

confidence: 99%

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Stochastic, structural and functional factors influencing AMPA and NMDA synaptic response variability: a review

2017

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Synaptic transmission is the basic mechanism of information transfer between neurons not only in the brain, but along all the nervous system. In this review we will briefly summarize some of the main parameters that produce stochastic variability in the synaptic response. This variability produces different effects on important brain phenomena, like learning and memory, and, alterations of its basic factors can cause brain malfunctioning.

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Section: Diffusion Model Of Glutamatementioning

confidence: 99%

Section: Pre-synaptic Factorsmentioning

confidence: 99%

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Stochastic, structural and functional factors influencing AMPA and NMDA synaptic response variability: a review

2017

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“…The extent of the occupancy depends on the properties of the AMPARs and the glutamate signal. Numerous models have been proposed to account for the activation of AMPA receptors (Raman and Trussell, 1992;Hausser and Roth, 1997;Rosenmund et al, 1998;Benke et al, 2001;Robert and Howe, 2003;Ventriglia and Di Maio, 2003). Studies of AMPARs from Purkinje cells have given rise to a model that provides a good description of the properties of AMPARs at PF synapses (Hausser and Roth, 1997), and we therefore used this for EPSC 1 in DGG, and [61.9, 3.7, 2.6] for EPSC 2 in DGG.…”

Section: Simulating the Effects Of Mvr And Ampar Saturationmentioning

confidence: 99%

The Influence of Multivesicular Release and Postsynaptic Receptor Saturation on Transmission at Granule Cell to Purkinje Cell Synapses

Foster¹,

Crowley²,

Regehr³

2005

J. Neurosci.

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The properties of a synapse are crucially dependent on whether an action potential can trigger the release of multiple vesicles at an individual release site [multivesicular release (MVR)] and whether fusion of a single vesicle leads to receptor saturation. MVR and receptor saturation both occur at some high p synapses, but it is not known whether they also occur at low p synapses. Here we examine this issue at the low p synapse between parallel fibers and Purkinje cells using the low-affinity antagonist DGG (␥-D-glutamylglycine) to relieve AMPA receptor saturation. We find that the presence of MVR and receptor saturation at this synapse alters the calcium dependence of synaptic transmission and reduces the extent of facilitation. These findings establish that MVR and postsynaptic receptor saturation can influence transmission even at synapses with a low initial probability of release and suggest that these properties may be common at synapses in the mammalian brain.

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“…The number N m of neurotransmitter molecules contained in each vesicle was computed by using concentration and volume data, by the Avogadro argument. This number was in the range 318-771 Di Maio 2000a,b, 2002;Ventriglia and Di Maio 2003b). We assumed that the molecules, being in thermal equilibrium with the water filling the vesicle, were distributed in the vesicle space uniformly and according to a Maxwell distribution in velocity.…”

Section: The Modelmentioning

confidence: 99%

Saturation in excitatory synapses of hippocampus investigated by computer simulations

Ventriglia

2004

Biol. Cybern.

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The standard view of the synaptic function in excitatory synapses has been deeply questioned by recent experimental data on hippocampal glutamate synapses both for possible receptor nonsaturation and for larger and non-Gaussian peak amplitude fluctuations. Our previous investigations of the mechanisms involved in the variability of the response of hippocampal glutamatergic synapses, carried out by computer simulation of simple Brownian models of glutamate diffusion, furnished initial evidence about their presynaptic character. A new, refined model, reported here, assumes a collision volume for the glutamate molecule and a more realistic description of receptors and their binding dynamics. Based on this model, conditions for AMPA and NMDA receptor saturation have been investigated and new miniature (or quantal) EPSC parameters have been computed. The results corroborate the hypothesis that the lack of AMPA and NMDA receptor saturation and the EPSC stochastic variability are attributable to the small volume of glutamatergic synaptic vesicles and hence to the small number of glutamate molecules diffusing in the cleft after a vesicle release. The investigations better characterize some not well-known elements of the synaptic structure, such as the fusion pore, and provide useful information on AMPA receptor dynamics. Indeed, a nice fit between computed EPSCs and some miniature EPSCs in recent experimental literature allowed for the computation of new transition time values among the different AMPA receptor states through a trial-and-error optimization procedure. Moreover, the model has been used to evaluate two hypotheses on the genesis of the long-term potentiation phenomenon.

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Stochastic fluctuations of the quantal EPSC amplitude in computer simulated excitatory synapses of hippocampus

Cited by 27 publications

References 26 publications

Stochastic, structural and functional factors influencing AMPA and NMDA synaptic response variability: a review

Stochastic, structural and functional factors influencing AMPA and NMDA synaptic response variability: a review

The Influence of Multivesicular Release and Postsynaptic Receptor Saturation on Transmission at Granule Cell to Purkinje Cell Synapses

Saturation in excitatory synapses of hippocampus investigated by computer simulations

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