Effect of Voltage Drop within the Synaptic Cleft on the Current and Voltage Generated at a Single Synapse

Savtchenko, Leonid P.; Antropov, S. N.; Коrogod, S. М.

doi:10.1016/s0006-3495(00)76670-7

Cited by 24 publications

(44 citation statements)

References 29 publications

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“…However, a recent theoretical investigation suggested that narrowing the cleft could significantly increase the effective cleft resistance. thus reducing the synaptic current (24), in line with the classical conjecture by Eccles (23). The present study investigates how these two phenomena interact, concluding that the synaptic cleft height may have an adaptive function of optimizing synaptic strength.…”

Section: Discussionsupporting

confidence: 87%

“…A similar phenomenon has been proposed to occur in central synapses (24). Could this counterbalance the effects of the increased neurotransmitter concentration in narrow clefts?…”

supporting

confidence: 52%

“…In the typical central synapse, the intracleft resistance could give rise to a significant voltage drop in the radial direction across the cleft, which in turn influences the local membrane potential V(r) (24). The receptor channel current could therefore depend on how far the activated receptor is located with respect to the cleft center/edge.…”

Section: Resultsmentioning

confidence: 99%

“…The membrane potential profile inside the synaptic cleft has been described in detail (24). In brief, the transmembrane voltage V(r, t) inside and outside the receptor (active) zone follows the equations, respectively: where c m is the membrane capacitance calculated per unitary radial increment at distance r from the center and R ex stands for the extracellular medium unit resistance.…”

mentioning

confidence: 99%

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The optimal height of the synaptic cleft

Savtchenko

Rusakov

2007

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

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151

181

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Signal integration in the brain is determined by the size and kinetics of rapid synaptic responses. The latter, in turn, depends on the concentration profile of neurotransmitter in the synaptic cleft. According to a traditional view, narrower clefts should correspond to higher intracleft concentrations of neurotransmitter, and therefore to the enhanced activation of synaptic receptors. Here, we argue that narrowing the cleft also increases electrical resistance of the intracleft medium and therefore reduces local receptor currents. We employ detailed theoretical analyses and Monte Carlo simulations to propose that these two contrasting phenomena result in a relatively narrow range of cleft heights at which the synaptic receptor current reaches its maximum. Over a physiological range of synaptic parameters, the ''optimum'' height falls between Ϸ12 and 20 nm. This range is consistent with the structure of central synapses reported by electron microscopy. Therefore, our results suggest that a simple fundamental principle may underlie the synaptic cleft architecture: to maximize synaptic strength.T he waveform of rapid synaptic responses shapes the temporal domain of signal integration in the brain (1, 2). In turn, the kinetics of synaptic receptor currents is constrained by diffusion of neurotransmitter in the synaptic cleft (3, 4). This relationship, however, remains poorly understood, mainly because events inside the cleft are beyond the powers of direct experimental observation. There is little doubt, however, that synaptic cleft geometry is an important factor in shaping synaptic currents (3, 5-7). The straightforward logic of physics predicts that decreasing the cleft height should increase the intracleft concentration of neurotransmitter and therefore enhance activation of synaptic receptors (8). In turn, increasing the lateral cleft size could generally slow down neurotransmitter escape from the cleft and thus prolong synaptic responses (9). Indeed, faster AMPA receptor-mediated EPSCs have recently been associated with smaller synaptic apposition zones in the developing cerebellar synapses (10). However, lateral dimensions of synapses fluctuate considerably (even within homogeneous synaptic populations), whereas the cleft height remains remarkably stable. For instance, at the common excitatory synapses in hippocampal area CA1, the lateral cleft area varies several-fold (11) whereas the cleft height shows the coefficient of variation (an upper estimate) of only Ϸ26% (12). Interestingly, osmotic challenge or other physiological manipulations that affect dramatically the overall extracellular space dimensions (13, 14) do not appear to modify the synaptic cleft height (15). This parameter also remains virtually unchanged during development (16-18). Remarkably, in electron micrographs of synaptosomes (a preparation obtained using strong mechanical forces of centrifugal separation), the distance between the apposing synaptic membranes is indistinguishable from that in the intact neuropil. Across many synaptic type...

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Section: Discussionsupporting

confidence: 87%

“…A similar phenomenon has been proposed to occur in central synapses (24). Could this counterbalance the effects of the increased neurotransmitter concentration in narrow clefts?…”

supporting

confidence: 52%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

The optimal height of the synaptic cleft

Savtchenko

Rusakov

2007

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

Self Cite

151

181

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show abstract

“…For the sake of simplicity we choose a model which combines the two processes: We consider a reversible binding-release reaction of ion channels with the cell skeleton and assume that this interaction induces a closing of the channels. Alternative models for pattern formation along the cell membrane take additional intermediate steps of the opening-closing dynamics into account [18,22,23,33] but a thorough analysis of the pattern formation processes in two spatial dimensions is not available yet.…”

Section: Introductionmentioning

confidence: 99%

Publisher's Note: Hexagonal, square, and stripe patterns of the ion channel density in biomembranes [Phys. Rev. E75, 016202 (2007)]

Hilt¹,

Zimmermann²

2007

Phys. Rev. E

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Transmembrane ion flow through channel proteins undergoing density fluctuations may cause lateral gradients of the electrical potential across the membrane giving rise to electrophoresis of charged channels. A model for the dynamics of the channel density and the voltage drop across the membrane (cable equation) coupled to a binding-release reaction with the cell skeleton (P. Fromherz and W. Zimmerman, Phys. Rev. E 51, R1659 (1995)) is analyzed in one and two spatial dimensions. Due to the binding release reaction spatially periodic modulations of the channel density with a finite wave number are favored at the onset of pattern formation, whereby the wave number decreases with the kinetic rate of the binding-release reaction. In a two-dimensional extended membrane hexagonal modulations of the ion channel density are preferred in a large range of parameters. The stability diagrams of the periodic patterns near threshold are calculated and in addition the equations of motion in the limit of a slow binding-release kinetics are derived.

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