Synaptic transmission at visualized sympathetic boutons: stochastic interaction between acetylcholine and its receptors

Bennett, Max R.; Farnell, L.; Gibson, W.G.; Lavidis, Nickolas A.

doi:10.1016/s0006-3495(97)78806-4

Cited by 32 publications

(45 citation statements)

References 41 publications

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“…3). The relative insensitivity of the O-state for nAChRs to variations in AChE densities in the vicinity of empirical measurements echoed those findings of previous Monte Carlo simulations in spatially synthetic conditions (19,20). …”

supporting

confidence: 77%

“…Here, we present an accurate three-dimensional (3D) model of synaptic topology with 9-nm resolution derived from electron tomography (5,16), combined with Monte Carlo reaction/diffusion algorithms (MCell, www.mcell.cnl.salk.edu) that use 3D random-walk diffusion steps while tracking the probabilistic interactions of individual molecules governed by kinetic rate constants (17)(18)(19)(20)(21)(22)(23)(24)(25). The model makes surprising predictions about the behavior of the two classes of nAChRs within functional microdomains and also provides evidence that synaptic transmission in the CG requires ectopic neurotransmitter release.…”

Section: Hhmi Author Manuscriptmentioning

confidence: 99%

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Evidence for Ectopic Neurotransmission at a Neuronal Synapse

Coggan

Bartol

Esquenazi

et al. 2005

Science

166

149

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Neurotransmitter release is well known to occur at specialized synaptic regions that include presynaptic active zones and postsynaptic densities. At cholinergic synapses in the chick ciliary ganglion, however, membrane formations and physiological measurements suggest that release distant from postsynaptic densities can activate the predominantly extrasynaptic α7 nicotinic receptor subtype. We explored such ectopic neurotransmission with a novel model synapse that combines Monte Carlo simulations with high-resolution serial electron microscopic tomography. Simulated synaptic activity is consistent with experimental recordings of miniature excitatory postsynaptic currents only when ectopic transmission is included in the model, broadening the possibilities for mechanisms of neuronal communication.Throughout the nervous system, release of synaptic vesicles from presynaptic nerve terminals is thought to be associated with pre-and post-synaptic specializations, including active zones (AZs) and postsynaptic densities (PSDs). Release of neurotransmitter vesicles at extrasynaptic sites (ectopic release) has been suggested by the presence of morphologically docked vesicles distant from PSDs in electron micrographs from tissues, including the ribbon synapses of bipolar neurons (1) and saccular hair cells (2). Recently, direct measurements of quantal release have been made from climbing fibers in the cerebellar cortex onto the closely apposed Bergmann glia (3). Despite these findings, there † To whom correspondence should be addressed: terry@salk.edu. * These authors contributed equally to this work. HHMI Author Manuscript HHMI Author Manuscript HHMI Author Manuscripthas been no demonstration of the participation of ectopic release of neurotransmitter in the course of interneuronal synaptic transmission.At the structurally complex and umbrella-like calyceal synapse of the ciliary ganglion (CG), the case for ectopic release has been growing. Two major classes of kinetically distinct nicotinic acetylcholine receptors (nAChRs) are spatially segregated in the CG (4-6). The α7-nAChRs are expressed on matted spines but are largely excluded from PSDs regardless of where they occur (7-9). The α3*-nAChRs (6) are primarily localized to PSDs (whether on spines or somatic membrane) but are present at lower density on non-PSD membrane (4,9,10). The α7-nAChRs exhibit profound desensitization, an order of magnitude faster decay time, and an open probability lower by a factor of 30 than that of α3*-nAChRs (11-13).The segregation of the two nAChR subtypes, especially the exclusion of α7-nAChRs from PSDs, has made it difficult to interpret physiological measurements that show that the α7-nAChRs account for the majority of current in evoked EPSCs (11,12), are necessary to sustain higher frequency throughput (11,14), and produce distinct Ca signals localized to spines (15). Images of presynaptic vesicles within docking distance (ready to release), as well as Ω profiles (the image capture of fusing vesicles), are seen throughout the ...

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supporting

confidence: 77%

Section: Hhmi Author Manuscriptmentioning

confidence: 99%

Evidence for Ectopic Neurotransmission at a Neuronal Synapse

Coggan

Bartol

Esquenazi

et al. 2005

Science

166

149

View full text Add to dashboard Cite

show abstract

“…The difference probably results from a difference in the number of receptors, as discussed by Rang (1981), Wathey et al (1979), and Bennett et al (1997). At punctate synapses diffusion is likely to dominate rebinding (Barbour, 2001).…”

Section: Intersynaptic Spillovermentioning

confidence: 99%

Mechanisms Shaping the Slow Nicotinic Synaptic Current at the Motoneuron-Renshaw Cell Synapse

d’Incamps

Krejci²,

Ascher³

2012

Journal of Neuroscience

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“…(1995). The distribution of rise times is used to yield an estimate of the e!ective di!usion constant D LCR "40 nm s\, which is in accordance with the range given by Kleinle et al (1996), Bennett et al (1997), Agmon &Edelstein (1997), andTrommershaK user et al (1999).…”

Section: Monte Carlo Simulations Of Epscsmentioning

confidence: 61%