scholarly journals Rapid active zone remodeling consolidates presynaptic potentiation

2018 ◽  
Author(s):  
Mathias A. Böhme ◽  
Anthony W. McCarthy ◽  
Andreas T. Grasskamp ◽  
Christine B. Beuschel ◽  
Pragya Goel ◽  
...  
Keyword(s):  
Neurotransmitter Release ◽  
Release Site ◽  
Scaffold Proteins ◽  
Homeostatic Plasticity ◽  
Discrete Subset ◽  
Molecular Sequence ◽  
Central Neurons ◽  
Presynaptic Plasticity ◽  
Active Zones ◽  
Plastic Changes

AbstractSynaptic transmission is mediated by neurotransmitter release at presynaptic active zones (AZs) followed by postsynaptic neurotransmitter detection. Plastic changes in transmission maintain functionality during perturbations and enable memory formation. Postsynaptic plasticity targets neurotransmitter receptors, but presynaptic plasticity mechanisms directly regulating the neurotransmitter release apparatus remain largely enigmatic. Here we describe that AZs consist of nano-modular release site units and identify a molecular sequence adding more modules within minutes of plasticity induction. This requires cognate transport machinery and a discrete subset of AZ scaffold proteins. Structural remodeling is not required for the immediate potentiation of neurotransmitter release, but rather necessary to sustain this potentiation over longer timescales. Finally, mutations in Unc13 that disrupt homeostatic plasticity at the neuromuscular junction also impair shot-term memory when central neurons are targeted, suggesting that both forms of plasticity operate via Unc13. Together, while immediate synaptic potentiation capitalizes on available material, it triggers the coincident incorporation of modular release sites to consolidate stable synapse function.

scholarly journals Neurotransmitter Release Site Replenishment and Presynaptic Plasticity

2020 ◽  
Vol 22 (1) ◽  
pp. 327
Author(s):  
Sumiko Mochida
Keyword(s):  
Neurotransmitter Release ◽  
Synaptic Vesicles ◽  
High Speed ◽  
Release Site ◽  
Short Term ◽  
Short Term Plasticity ◽  
Multiple Protein ◽  
Presynaptic Plasticity ◽  
Presynaptic Plasma Membrane ◽  
Ca2 Channels

An action potential (AP) triggers neurotransmitter release from synaptic vesicles (SVs) docking to a specialized release site of presynaptic plasma membrane, the active zone (AZ). The AP simultaneously controls the release site replenishment with SV for sustainable synaptic transmission in response to incoming neuronal signals. Although many studies have suggested that the replenishment time is relatively slow, recent studies exploring high speed resolution have revealed SV dynamics with milliseconds timescale after an AP. Accurate regulation is conferred by proteins sensing Ca2+ entering through voltage-gated Ca2+ channels opened by an AP. This review summarizes how millisecond Ca2+ dynamics activate multiple protein cascades for control of the release site replenishment with release-ready SVs that underlie presynaptic short-term plasticity.

scholarly journals (M)Unc13s in Active Zone Diversity: A Drosophila Perspective

2022 ◽  
Vol 13 ◽  
Author(s):  
Chengji Piao ◽  
Stephan J. Sigrist
Keyword(s):  
Synaptic Vesicle ◽  
Active Zone ◽  
Stoichiometric Composition ◽  
Release Site ◽  
Homeostatic Plasticity ◽  
Release Factor ◽  
Loosely Coupled ◽  
Action Potential Frequency ◽  
Active Zones ◽  
Potential Frequency

The so-called active zones at pre-synaptic terminals are the ultimate filtering devices, which couple between action potential frequency and shape, and the information transferred to the post-synaptic neurons, finally tuning behaviors. Within active zones, the release of the synaptic vesicle operates from specialized “release sites.” The (M)Unc13 class of proteins is meant to define release sites topologically and biochemically, and diversity between Unc13-type release factor isoforms is suspected to steer diversity at active zones. The two major Unc13-type isoforms, namely, Unc13A and Unc13B, have recently been described from the molecular to the behavioral level, exploiting Drosophila being uniquely suited to causally link between these levels. The exact nanoscale distribution of voltage-gated Ca2+ channels relative to release sites (“coupling”) at pre-synaptic active zones fundamentally steers the release of the synaptic vesicle. Unc13A and B were found to be either tightly or loosely coupled across Drosophila synapses. In this review, we reported recent findings on diverse aspects of Drosophila Unc13A and B, importantly, their nano-topological distribution at active zones and their roles in release site generation, active zone assembly, and pre-synaptic homeostatic plasticity. We compared their stoichiometric composition at different synapse types, reviewing the correlation between nanoscale distribution of these two isoforms and release physiology and, finally, discuss how isoform-specific release components might drive the functional heterogeneity of synapses and encode discrete behavior.

scholarly journals Endogenous tagging reveals differential regulation of Ca2+ channels at single AZs during presynaptic homeostatic potentiation and depression

2017 ◽  
Author(s):  
Scott J. Gratz ◽  
Pragya Goel ◽  
Joseph J. Bruckner ◽  
Roberto X. Hernandez ◽  
Karam Khateeb ◽  
...  
Keyword(s):  
Information Flow ◽  
Neurotransmitter Release ◽  
Synaptic Strength ◽  
Live Imaging ◽  
Differential Regulation ◽  
Synaptic Function ◽  
Homeostatic Plasticity ◽  
Multiple Forms ◽  
Active Zones ◽  
Ca2 Channels

AbstractNeurons communicate through Ca2+-dependent neurotransmitter release at presynaptic active zones (AZs). Neurotransmitter release properties play a key role in defining information flow in circuits and are tuned during multiple forms of plasticity. Despite their central role in determining neurotransmitter release properties, little is known about how Ca2+ channel levels are modulated to calibrate synaptic function. We used CRISPR to tag the Drosophila CaV2 Ca2+ channel Cacophony (Cac) and investigated the regulation of endogenous Ca2+ channels during homeostatic plasticity in males in which all endogenous Cac channels are tagged. We found that heterogeneously distributed Cac is highly predictive of neurotransmitter release probability at individual AZs and differentially regulated during opposing forms of presynaptic homeostatic plasticity. Specifically, Cac levels at AZ are increased during chronic and acute presynaptic homeostatic potentiation (PHP), and live imaging during acute expression of PHP reveals proportional Ca2+ channel accumulation across heterogeneous AZs. In contrast, endogenous Cac levels do not change during presynaptic homeostatic depression (PHD), implying that the reported reduction in Ca2+ influx during PHD is achieved through functional adaptions to pre-existing Ca2+ channels. Thus, distinct mechanisms bi-directionally modulate presynaptic Ca2+ levels to maintain stable synaptic strength in response to diverse challenges, with Ca2+ channel abundance providing a rapidly tunable substrate for potentiating neurotransmitter release over both acute and chronic timescales.

RIM proteins and their role in synapse function

2010 ◽  
Vol 391 (6) ◽  
Author(s):  
Tobias Mittelstaedt ◽  
Elena Alvaréz-Baron ◽  
Susanne Schoch
Keyword(s):  
Synaptic Vesicle ◽  
Active Zone ◽  
Neurotransmitter Release ◽  
Multidomain Proteins ◽  
Short Term ◽  
Presynaptic Nerve Terminal ◽  
Presynaptic Plasticity ◽  
Active Zones ◽  
Synaptic Vesicle Release ◽  
The Brain

Abstract Active zones are specialized areas of the plasma membrane in the presynaptic nerve terminal that mediate neurotransmitter release and synaptic plasticity. The multidomain proteins RIM1 and RIM2 are integral components of the cytomatrix at the active zone, interacting with most other active zone-enriched proteins as well as synaptic vesicle proteins. In the brain, RIMs are present in multiple isoforms (α, β, γ) diverging in their structural composition, which mediate overlapping and distinct functions. Here, we summarize recent findings about the specific roles of the various RIM isoforms in basic synaptic vesicle release as well as long- and short-term presynaptic plasticity.

scholarly journals Rapid homeostatic modulation of transsynaptic nanocolumn rings

2021 ◽  
Author(s):  
Paola Muttathukunnel ◽  
Patrick Frei ◽  
Sarah Perry ◽  
Dion Dickman ◽  
Martin Mueller
Keyword(s):  
Glutamate Receptor ◽  
Neurotransmitter Release ◽  
Information Transfer ◽  
Stimulated Emission ◽  
Homeostatic Plasticity ◽  
Synaptic Efficacy ◽  
Molecular Architecture ◽  
Neural Information ◽  
Active Zones ◽  
Chemical Synapses

Robust neural information transfer relies on a delicate molecular nano-architecture of chemical synapses. Neurotransmitter release is controlled by a specific arrangement of proteins within presynaptic active zones. How the specific presynaptic molecular architecture relates to postsynaptic organization, and how synaptic nano-architecture is transsynaptically regulated to achieve stable synaptic transmission remains enigmatic. Using time-gated stimulated emission depletion (gSTED) microscopy at the Drosophila neuromuscular junction, we here find that presynaptic nano-rings formed by the active-zone scaffold Bruchpilot (Brp) precisely align with postsynaptic glutamate receptor (GluR) rings. Individual rings harbor ~5 transsynaptically-aligned Brp-GluR nanocolumns. Intriguingly, acute GluR impairment rapidly triggers the formation of new transsynaptic nanocolumns on the minute time scale during homeostatic plasticity. We reveal distinct phases of structural transsynaptic homeostatic plasticity, with postsynaptic reorganization preceding presynaptic modulation. Finally, the auxiliary GluR subunit Neto-B; promotes structural and functional homeostatic plasticity. Thus, transsynaptic nanocolumns arrange in stereotypic rings that are rapidly modulated during homeostatic plasticity to stabilize synaptic efficacy.

scholarly journals The auxiliary glutamate receptor subunit dSol-1 promotes presynaptic neurotransmitter release and homeostatic potentiation

2020 ◽  
Vol 117 (41) ◽  
pp. 25830-25839
Author(s):  
Beril Kiragasi ◽  
Pragya Goel ◽  
Sarah Perry ◽  
Yifu Han ◽  
Xiling Li ◽  
...  
Keyword(s):  
Neurotransmitter Release ◽  
Homeostatic Regulation ◽  
Auxiliary Subunits ◽  
Auxiliary Subunit ◽  
Glutamate Receptor Subunit ◽  
Synaptic Functions ◽  
Cub Domain ◽  
Active Zones ◽  
Domain Protein ◽  
Dependent Mechanism

Presynaptic glutamate receptors (GluRs) modulate neurotransmitter release and are physiological targets for regulation during various forms of plasticity. Although much is known about the auxiliary subunits associated with postsynaptic GluRs, far less is understood about presynaptic auxiliary GluR subunits and their functions. At theDrosophilaneuromuscular junction, a presynaptic GluR,DKaiR1D, localizes near active zones and operates as an autoreceptor to tune baseline transmission and enhance presynaptic neurotransmitter release in response to diminished postsynaptic GluR functionality, a process referred to as presynaptic homeostatic potentiation (PHP). Here, we identify an auxiliary subunit that collaborates with DKaiR1D to promote these synaptic functions. This subunit, dSol-1, is the homolog of theCaenorhabditis elegansCUB (Complement C1r/C1s, Uegf, Bmp1) domain protein Sol-1. We find thatdSol-1functions in neurons to facilitate baseline neurotransmission and to enable PHP expression, properties shared withDKaiR1D. Intriguingly, presynaptic overexpression ofdSol-1is sufficient to enhance neurotransmitter release through aDKaiR1D-dependent mechanism. Furthermore,dSol-1is necessary to rapidly increase the abundance of DKaiR1D receptors near active zones during homeostatic signaling. Together with recent work showing the CUB domain protein Neto2 is necessary for the homeostatic modulation of postsynaptic GluRs in mammals, our data demonstrate that dSol-1 is required for the homeostatic regulation of presynaptic GluRs. Thus, we propose that CUB domain proteins are fundamental homeostatic modulators of GluRs on both sides of the synapse.

Neurotransmitter Release: Priming at Presynaptic Active Zones

2008 ◽  
pp. 2834-2839
Author(s):  
Hiroshi Kawabe ◽  
Frederique Varoqueaux ◽  
Nils Brose
Keyword(s):  
Neurotransmitter Release ◽  
Active Zones

Vesicle release site organization at synaptic active zones

2018 ◽  
Vol 127 ◽  
pp. 3-13 ◽  
Author(s):  
Alexander M. Walter ◽  
Mathias A. Böhme ◽  
Stephan J. Sigrist
Keyword(s):  
Release Site ◽  
Vesicle Release ◽  
Active Zones
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