Neuromuscular transmission at an active zone: the secretosome hypothesis

Bennett, Max R.

doi:10.1007/bf02284848

Cited by 18 publications

(6 citation statements)

References 108 publications

(96 reference statements)

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“…Recent studies have used a combination of electrophysiology, imaging, and computer modeling to suggest that AZs of synapses may be constructed by differential assembly of unitary building blocks, so-called single vesicle release sites (Tarr et al 2013b) akin to the "secretosome" described by Bennett (1996). These single vesicle release sites consist of a synaptic vesicle and a small number of associated VGCCs (Luo et al 2015;Tarr et al 2013b), and their arrangement into AZs directly affects synaptic release and facilitation.…”

Section: Discussionmentioning

confidence: 99%

Transmitter release site organization can predict synaptic function at the neuromuscular junction

Laghaei

Tarr

et al. 2018

Journal of Neurophysiology

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We have investigated the impact of transmitter release site (active zone; AZ) structure on synaptic function by physically rearranging the individual AZ elements in a previously published frog neuromuscular junction (NMJ) AZ model into the organization observed in a mouse NMJ AZ. We have used this strategy, purposefully without changing the properties of AZ elements between frog and mouse models (even though there are undoubtedly differences between frog and mouse AZ elements in vivo), to directly test how structure influences function at the level of an AZ. Despite a similarly ordered ion channel array substructure within both frog and mouse AZs, frog AZs are much longer and position docked vesicles in a different location relative to AZ ion channels. Physiologically, frog AZs have a lower probability of transmitter release compared with mouse AZs, and frog NMJs facilitate strongly during short stimulus trains in contrast with mouse NMJs that depress slightly. Using our computer modeling approach, we found that a simple rearrangement of the AZ building blocks of the frog model into a mouse AZ organization could recapitulate the physiological differences between these two synapses. These results highlight the importance of simple AZ protein organization to synaptic function. NEW & NOTEWORTHY A simple rearrangement of the basic building blocks in the frog neuromuscular junction model into a mouse transmitter release site configuration predicted the major physiological differences between these two synapses, suggesting that transmitter release site structure and organization is a strong predictor of function.

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Section: Discussionmentioning

confidence: 99%

Transmitter release site organization can predict synaptic function at the neuromuscular junction

Laghaei

Tarr

et al. 2018

Journal of Neurophysiology

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“…1B). The core complex, regulatory proteins, and calcium channel are thought to be mutually linked, and the entire ensemble is sometimes referred to as a secretosome (Bennett 1996). Regulatory molecules and calcium receptors are also present, generating complex molecular interactions (Wu et al 1999).…”

Section: Synapsementioning

confidence: 99%

Silent Synapses in Neural Plasticity: Current Evidence

Atwood

Wojtowicz²

1999

Learning &Amp; Memory

117

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Silent synapses, defined as structural specializations for neurotransmission that do not produce a physiological response in the receiving cell, may occur frequently in neural circuits. Their recruitment to physiological effectiveness may be an important component of circuit modification. In several nervous systems, evidence from electrophysiological and optophysiological measurements has established a strong case for the existence of silent synapses and for their emergence as active synapses with appropriate stimulation. During normal development and aging, synapses of individual neurons change in number, and many of these may be functionally silent at certain stages of their developmental trajectory. Changes in their status may contribute to shaping the properties of neural pathways during development, often in response to neural activity. In general, it is often difficult to distinguish physiological emergence of pre-established silent synapses from developmental maturation or de novo formation of new synapses. Several possible mechanisms for silent synapses and their recruitment are reviewed. These include incompletely assembled synapses that lack structural components, insufficient availability of key presynaptic proteins, and nonfunctional postsynaptic receptors, or presence of receptors that do not mediate a postsynaptic response except under specific conditions (conditionally silent synapses). The available silent synapses can often be rapidly activated, and conversely, active synapses appear to be rapidly silenced in many instances. These properties enable silent synapses to participate in short-term facilitation and depression. In addition, they may contribute to long-term facilitation and potentiation, especially during development.

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“…The generally accepted notion of the synapse as a ''gap'' between one cell and another across which signals were propagated came from considerations of how muscle contractions are initiated by the nerve fibers impinging on them [1]. Once it was established that the nerve fibers responsible for muscle contractions originate in nerve cells and that they propagate electrical signals to muscles with a measurable delay across what must be an intercellular gap, questions arose as to whether the same relationship existed between nerve fibers and nerve cells.…”

Section: Introductionmentioning

confidence: 99%

The CNS Synapse Revisited: Gaps, Adhesive Welds, and Borders

Latefi

Colman

2006

Neurochem Res

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Although processes leading up to the point of synapse formation are fairly well understood, the precise sequence of events in which the membranes of two separate cells "lock in" to form a mature synaptic junctional complex is poorly understood. A careful study of the molecules operating at the synapse indicates that their roles are more multifarious than once imagined. In this review we posit that the synapse is a functional organelle with poorly defined boundaries and a complex biochemistry. The role of adhesion molecules, including the integration of their signaling and adhesive properties in the context of synaptic activity is discussed.

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Neuromuscular transmission at an active zone: the secretosome hypothesis

Cited by 18 publications

References 108 publications

Transmitter release site organization can predict synaptic function at the neuromuscular junction

Transmitter release site organization can predict synaptic function at the neuromuscular junction

Silent Synapses in Neural Plasticity: Current Evidence

The CNS Synapse Revisited: Gaps, Adhesive Welds, and Borders

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