Preferential Localization of Glutamate Receptors Opposite Sites of High Presynaptic Release

Marrus, Scott B.; DiAntonio, Aaron

doi:10.1016/j.cub.2004.05.047

Cited by 96 publications

(91 citation statements)

References 27 publications

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“…In addition, we also used a model with two pools of release-ready vesicles and heterogeneous release probabilities (model 2) (see Fig. 8 A) (Sakaba and Neher, 2001;Marrus and DiAntonio, 2004). In model 2, a small pool of release-ready vesicles (N 2 ) with a high vesicular release probability ( p vr2 ) is refilled from a larger pool (N 1 ), which has a lower vesicular release probability ( p vr1 ) and which, in turn, is refilled from a supply pool (N 0 ).…”

Section: Methodsmentioning

confidence: 99%

Rapid Active Zone Remodeling during Synaptic Plasticity

Weyhersmüller

Hallermann²,

Wagner³

et al. 2011

J. Neurosci.

169

226

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How can synapses change the amount of neurotransmitter released during synaptic plasticity? Although release in general is intensely investigated, its determinants during plasticity are still poorly understood. As a model for plastic strengthening of synaptic release, we here use the well-established presynaptic homeostatic compensation during interference with postsynaptic glutamate receptors at the Drosophila neuromuscular junction. Combining short-term plasticity analysis, cumulative EPSC analysis, fluctuation analysis, and quantal short-term plasticity modeling, we found an increase in the number of release-ready vesicles during presynaptic strengthening. High-resolution light microscopy revealed an increase in the amount of the active zone protein Bruchpilot and an enlargement of the presynaptic cytomatrix structure. Furthermore, these functional and structural alterations of the active zone were not only observed after lifelong but already after minutes of presynaptic strengthening. Our results demonstrate that presynaptic plasticity can induce active zone remodeling, which regulates the number of release-ready vesicles within minutes.

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Section: Methodsmentioning

confidence: 99%

Rapid Active Zone Remodeling during Synaptic Plasticity

Weyhersmüller

Hallermann²,

Wagner³

et al. 2011

J. Neurosci.

169

226

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“…At control NMJs, diffraction-limited BRP spots mark individual active zones 21 that appear as ring-shaped structures when imaged at higher resolutions with STED 20,22 (Fig. 2g,h).…”

Section: Similar Synaptic Phenotypes Of Syd-1 Nrx-1 and Nlg1mentioning

confidence: 99%

Cooperation of Syd-1 with Neurexin synchronizes pre- with postsynaptic assembly

et al. 2012

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Understanding the process of synapse assembly in molecular and cell-biological detail is a prerequisite for understanding neural circuit development and activity-mediated remodeling, and thus is important for unraveling learning and memory processes (structural plasticity) [1][2][3] . Functional chemical synapses are characterized by two apposed compartments that must be coestablished with high spatiotemporal precision: the presynaptic active zone, where regulated and rapid fusion of neurotransmitter-filled synaptic vesicles takes place, and the postsynaptic density (PSD), which embeds neurotransmitter receptors.Glutamatergic neuromuscular junction (NMJ) terminals of Drosophila larvae grow to meet the requirements of the growing muscle fibers, a process in which new synapses are continuously added 4 (where a synapse is defined as a single active zone opposed by a single PSD 1 ). In vivo imaging has shown that presynaptic Syd-1 and Liprin-α clusters initiate active zone formation 5 . On the postsynaptic side, initial PSD growth depends on incorporation of a glutamate receptor (GluR) containing the GluRIIA subunit. Later PSD maturation is marked by the incorporation of GluRIIB-containing receptor complexes 6 . Synapse assembly is concluded at presynaptic active zones by the incorporation of the active zone scaffold component Bruchpilot (BRP) 5 .Coordinating synapse assembly requires signaling across the synaptic cleft, which separates pre-from postsynaptic membranes. Transsynaptic cell adhesion molecules are obvious candidates for coupling active zone and PSD assembly. In vitro, the Neurexin-Neuroligin (Nrx-Nlg) complex can mediate the trans-synaptic signaling required for synapse assembly 7,8 . How this signaling axis integrates with the additional assembly machinery, however, has remained largely unclear.Here, we provide evidence of a dual role for Syd-1 in early assembly of NMJ synapses. It retains Liprin-α clusters at active zones and is important for clustering of presynaptic Nrx-1, likely through a direct and PDZ-domain-dependent interaction. Consequently, Syd-1 is also needed for clustering of postsynaptic Nlg1, which organizes postsynaptic assembly. Coincident action of Syd-1 with Nrx-1-Nlg1 appears to allow active zone scaffolds to pass through an initial, still fragile assembly phase. We suggest that binding between Syd-1 and Nrx-1-Nlg1 is a means to coordinate pre-with postsynaptic assembly. Our study shows an example of how coincident action of a presynaptic active zone scaffold protein and a trans-synaptic cell adhesion protein module can spatiotemporally orchestrate synapse assembly. RESULTSInitially described in cell culture systems (for a review, see ref. 9), interaction between mammalian presynaptic Nrx proteins and postsynaptic Nlg molecules was proposed to be important for proper synapse assembly. However, genetic ablation of three Nlg (Nlgn) genes in mice 10 does not result in a substantial structural phenotype, potentially reflecting a strong capacity for compensatory processes in vivo.Nonethe...

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“…During the first 2 h of synaptogenesis, glutamate receptors begin to accumulate on the postsynaptic surface. Electrophysiological measurements on embryos (16,17) show low background activity at the synapse, as well as a larger response to applied electrical fields. The background activity is Author contributions: S.S., S.Y., A.C., and T.S.…”

mentioning

confidence: 97%

Mechanical tension contributes to clustering of neurotransmitter vesicles at presynaptic terminals

Siechen¹,

Yang

Chiba

et al. 2009

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

153

145

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Memory and learning in animals are mediated by neurotransmitters that are released from vesicles clustered at the synapse. As a synapse is used more frequently, its neurotransmission efficiency increases, partly because of increased vesicle clustering in the presynaptic neuron. Vesicle clustering has been believed to result primarily from biochemical signaling processes that require the connectivity of the presynaptic terminal with the cell body, the central nervous system, and the postsynaptic cell. Our in vivo experiments on the embryonic Drosophila nervous system show that vesicle clustering at the neuromuscular presynaptic terminal depends on mechanical tension within the axons. Vesicle clustering vanishes upon severing the axon from the cell body, but is restored when mechanical tension is applied to the severed end of the axon. Clustering increases when intact axons are stretched mechanically by pulling the postsynaptic muscle. Using micro mechanical force sensors, we find that embryonic axons that have formed neuromuscular junctions maintain a rest tension of Ϸ1 nanonewton. If the rest tension is perturbed mechanically, axons restore the rest tension either by relaxing or by contracting over a period of Ϸ15 min. Our results suggest that neuromuscular synapses employ mechanical tension as a signal to modulate vesicle accumulation and synaptic plasticity.T he accumulation of neurotransmitter containing vesicles at the presynaptic terminal is essential for neural communication. On the arrival of an action potential at the terminal, neurotransmitters are released through exocytosis of the vesicles. The transmitters excite the postsynaptic terminal in a millisecond time frame (1). The amount of neurotransmitter release for a given action potential depends on several factors including how frequently the synapse has been used. This usage dependent plasticity is believed to be the basis of memory and learning (2). Despite a wealth of knowledge on the molecular components of the synapse (3, 4) and the modulation of the postsynaptic machinery during long-term potentiation and depression (5-7), the mechanism of vesicle accumulation at the presynaptic terminal and regulation of neurotransmission in a usage-dependent manner remains unclear (8). There is increasing experimental evidence suggesting that the mechanical microenvironment has a significant influence on a variety of cell functions including gene expression, cell growth and morphology, cytoskeletal organization, and apoptosis (9-13). Our in vivo experiments reveal that mechanical tension in axons plays a key role in vesicle accumulation.We examine the neuromuscular synapse within live embryos of Drosophila melanogaster (14) (Fig. 1A). In Drosophila, an aCC (anterior corner cell) pioneer motoneuron extends a single axon and invariably innervates its target, muscle1. A pair of aCC motoneurons occurs in every segment of the embryo, and their development is highly stereotyped. The first contact between the aCC axon and muscle1 occurs at hour 14 of embryogenesis, ...

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Preferential Localization of Glutamate Receptors Opposite Sites of High Presynaptic Release

Abstract: When confronted with an array of active zones, glutamate receptors preferentially cluster opposite the largest and most physiologically active sites. These results suggest an activity-dependent matching of pre- and postsynaptic function at the level of a single active zone.

Cited by 96 publications

References 27 publications

Rapid Active Zone Remodeling during Synaptic Plasticity

Rapid Active Zone Remodeling during Synaptic Plasticity

Cooperation of Syd-1 with Neurexin synchronizes pre- with postsynaptic assembly

Mechanical tension contributes to clustering of neurotransmitter vesicles at presynaptic terminals

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