A Brownian model of glutamate diffusion in excitatory synapses of hippocampus

Ventriglia, Francesco; Maio, Vito Di

doi:10.1016/s0303-2647(00)00108-8

Cited by 28 publications

(28 citation statements)

References 21 publications

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“…Although the structure of the glutaminergic synapse appears to be simple in principle, its geometry and the diffusion of transmitters have several infrastructure limitations that need to be accounted for in a correct simulation [6][7][8][9][10][11][12][13]. Several models oversimplify the synaptic space, and the diffusion mechanism, just assuming the instantaneous release of a given amount of glutamate molecules at the top of a parallelpiped, and an array of receptors at its bottom [14,15].…”

Section: Geometry Of the Synaptic Spacementioning

confidence: 99%

“…The position (x,y) on the plane plays an important role in the shaping the time course and amplitude of the post-synaptic response [11,29]. The vesicle is assumed of spheric shape with an inner mean diameter of 12 nm and filled with different numbers of molecules depending on the concentration of glutamate [10,11,14,22,23,30,31].…”

Section: Geometry Of the Synaptic Spacementioning

confidence: 99%

“…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%

“…Each position i,j ∈ R may or may not contain a receptor (1 for AMPAR, 2 for NMDAR and 0 for empty position). The corners of the square matrix, never contain receptors to respect the circular shape of the PSD (see for example Figure 2 in [10]). The relative AMPAR and NMDAR position i,j ∈ R is always chosen randomly.…”

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%

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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: Geometry Of the Synaptic Spacementioning

confidence: 99%

Section: Geometry Of the Synaptic Spacementioning

confidence: 99%

Section: Diffusion Model Of Glutamatementioning

confidence: 99%

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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Ultrastructural organization of lamprey reticulospinal synapses in three dimensions

Gustafsson

Birinyi

Crum

et al. 2002

J of Comparative Neurology

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The giant reticulospinal synapse in lamprey provides a unique model to study synaptic vesicle traffic. The axon permits microinjections, and the active zones are often separated from each other, which makes it possible to track vesicle cycling at individual release sites. However, the proportion of reticulospinal synapses with individual active zones ("simple synapses") is unknown and a quantitative description of their organization is lacking. Here, we report such data obtained by serial section analysis, intermediate-voltage electron microscopy, and electron tomography. The simple synapse was the most common type (78%). It consisted of one active zone contacting one dendritic process. The remaining synapses were "complex," mostly containing one vesicle cluster and two to three active zones synapsing with distinct dendritic shafts. Occasional axosomatic synapses with multiple active zones forming synapses with the same cell were also observed. The vast majority of active zones in all synapse types contained both chemical and electrotonic synaptic specializations. Quantitative analysis of simple synapses showed that the majority had active zones with a diameter of 0.8-1.8 microm. The number of synaptic vesicles and the height of the vesicle cluster in middle sections of serially cut synapses correlated with the active zone length within, but not above, this size range. Electron tomography of simple synapses revealed small filaments between the clustered synaptic vesicles. A single vesicle could be in contact with up to 12 filaments. Another type of filament, also associated with synaptic vesicles, emerged from dense projections. Up to six filaments could be traced from one dense projection.

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Local Chemical Stimulation of Neurons with the Fluidic Force Microscope (FluidFM)

et al. 2017

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Physiological communication between neurons is dependent on the exchange of neurotransmitters at the synapses. Although this chemical signal transmission targets specific receptors and allows for subtle adaptation of the action potential, in vitro neuroscience typically relies on electrical currents and potentials to stimulate neurons. The electric stimulus is unspecific and the confinement of the stimuli within the media is technically difficult to control and introduces large artifacts in electric recordings of the activity. Here, we present a local chemical stimulation platform that resembles in vivo physiological conditions and can be used to target specific receptors of synapses. Neurotransmitters were dispensed using the force-controlled fluidic force microscope (FluidFM) nanopipette, which provides exact positioning and precise liquid delivery. We show that controlled release of the excitatory neurotransmitter glutamate induces spiking activity in primary rat hippocampal neurons, as measured by concurrent electrical and optical recordings using a microelectrode array and a calcium-sensitive dye, respectively. Furthermore, we characterized the glutamate dose response of neurons by applying stimulation pulses of glutamate with concentrations from 0 to 0.5 mm. This new stimulation approach, which combines FluidFM for gentle and precise positioning with a microelectrode array read-out, makes it possible to modulate the activity of individual neurons chemically and simultaneously record their induced activity across the entire neuronal network. The presented platform not only offers a more physiological alternative compared with electrical stimulation, but also provides the possibility to study the effects of the local application of neuromodulators and other drugs.

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A Brownian model of glutamate diffusion in excitatory synapses of hippocampus

Cited by 28 publications

References 21 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

Ultrastructural organization of lamprey reticulospinal synapses in three dimensions

Local Chemical Stimulation of Neurons with the Fluidic Force Microscope (FluidFM)

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