scholarly journals Short-Term Presynaptic Plasticity

2012 ◽  
Vol 4 (7) ◽  
pp. a005702-a005702 ◽  
Author(s):  
W. G. Regehr
Keyword(s):  
Short Term ◽  
Presynaptic Plasticity

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 Control of neurotransmitter release by two distinctmembrane-binding faces of the Munc13-1 C­1C2B region

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Marcial Camacho ◽  
Bradley Quade ◽  
Thorsten Trimbuch ◽  
Junjie Xu ◽  
Levent Sari ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Neurotransmitter Release ◽  
Synaptic Vesicles ◽  
Point Mutations ◽  
Short Term ◽  
In Vitro Reconstitution ◽  
Presynaptic Plasticity ◽  
Hippocampal Cultures

Munc13-1 plays a central role in neurotransmitter release through its conserved C-terminal region, which includes a diacyglycerol (DAG)-binding C1 domain, a Ca2+/PIP2-binding C2B domain, a MUN domain and a C2C domain. Munc13-1 was proposed to bridge synaptic vesicles to the plasma membrane through distinct interactions of the C­1C2B region with the plasma membrane: i) one involving a polybasic face that is expected to yield a perpendicular orientation of Munc13-1 and hinder release; and ii) another involving the DAG-Ca2+-PIP2-binding face that is predicted to result in a slanted orientation and facilitate release. Here we have tested this model and investigated the role of the C­1C2B region in neurotransmitter release. We find that K603E or R769E point mutations in the polybasic face severely impair Ca2+-independent liposome bridging and fusion in in vitro reconstitution assays, and synaptic vesicle priming in primary murine hippocampal cultures. A K720E mutation in the polybasic face and a K706E mutation in the C2B domain Ca2+-binding loops have milder effects in reconstitution assays and do not affect vesicle priming, but enhance or impair Ca2+-evoked release, respectively. The phenotypes caused by combining these mutations are dominated by the K603E and R769E mutations. Our results show that the C1-C2B region of Munc13-1 plays a central role in vesicle priming and support the notion that two distinct faces of this region control neurotransmitter release and short-term presynaptic plasticity.

scholarly journals Action potential-coupled Rho GTPase signaling drives presynaptic plasticity

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Shataakshi Dube O'Neil ◽  
Bence Rácz ◽  
Walter Evan Brown ◽  
Yudong Gao ◽  
Erik J Soderblom ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Rho Gtpase ◽  
Calcium Influx ◽  
Inhibitory Synapses ◽  
Fluorescence Lifetime Imaging ◽  
Short Term ◽  
Adult Mice ◽  
Rac1 Activity ◽  
Presynaptic Plasticity

In contrast to their postsynaptic counterparts, the contributions of activity-dependent cytoskeletal signaling to presynaptic plasticity remain controversial and poorly understood. To identify and evaluate these signaling pathways, we conducted a proteomic analysis of the presynaptic cytomatrix using in vivo biotin identification (iBioID). The resultant proteome was heavily enriched for actin cytoskeleton regulators, including Rac1, a Rho GTPase that activates the Arp2/3 complex to nucleate branched actin filaments. Strikingly, we find Rac1 and Arp2/3 are closely associated with synaptic vesicle membranes in adult mice. Using three independent approaches to alter presynaptic Rac1 activity (genetic knockout, spatially restricted inhibition, and temporal optogenetic manipulation), we discover that this pathway negatively regulates synaptic vesicle replenishment at both excitatory and inhibitory synapses, bidirectionally sculpting short-term synaptic depression. Finally, we use two-photon fluorescence lifetime imaging to show that presynaptic Rac1 activation is coupled to action potentials by voltage-gated calcium influx. Thus, this study uncovers a previously unrecognized mechanism of actin-regulated short-term presynaptic plasticity that is conserved across excitatory and inhibitory terminals. It also provides a new proteomic framework for better understanding presynaptic physiology, along with a blueprint of experimental strategies to isolate the presynaptic effects of ubiquitously expressed proteins.

scholarly journals Mechanistic insights into neurotransmitter release and presynaptic plasticity from the crystal structure of Munc13-1 C1C2BMUN

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Junjie Xu ◽  
Marcial Camacho ◽  
Yibin Xu ◽  
Victoria Esser ◽  
Xiaoxia Liu ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Binding Sites ◽  
Neurotransmitter Release ◽  
Synaptic Vesicles ◽  
Plasma Membranes ◽  
Helical Structure ◽  
Membrane Interface ◽  
Short Term ◽  
Presynaptic Plasticity ◽  
Multiple Domains

Munc13–1 acts as a master regulator of neurotransmitter release, mediating docking-priming of synaptic vesicles and diverse presynaptic plasticity processes. It is unclear how the functions of the multiple domains of Munc13–1 are coordinated. The crystal structure of a Munc13–1 fragment including its C1, C2B and MUN domains (C1C2BMUN) reveals a 19.5 nm-long multi-helical structure with the C1 and C2B domains packed at one end. The similar orientations of the respective diacyglycerol- and Ca2+-binding sites of the C1 and C2B domains suggest that the two domains cooperate in plasma-membrane binding and that activation of Munc13–1 by Ca2+ and diacylglycerol during short-term presynaptic plasticity are closely interrelated. Electrophysiological experiments in mouse neurons support the functional importance of the domain interfaces observed in C1C2BMUN. The structure imposes key constraints for models of neurotransmitter release and suggests that Munc13–1 bridges the vesicle and plasma membranes from the periphery of the membrane-membrane interface.

scholarly journals Control of neurotransmitter release and presynaptic plasticity by re-orientation of membrane-bound Munc13-1

2021 ◽  
Author(s):  
Josep Rizo ◽  
Marcial Camacho ◽  
Bradley Quade ◽  
Thorsten Trimbuch ◽  
Junjie Xu ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Neurotransmitter Release ◽  
Point Mutations ◽  
Short Term ◽  
In Vitro Reconstitution ◽  
C1 Domain ◽  
Presynaptic Plasticity ◽  
Membrane Bound

Munc13-1 plays a central role in neurotransmitter release through its conserved C-terminal region, which includes a diacyglycerol (DAG)-binding C1 domain, a Ca2+/PIP2-binding C2B domain, a MUN domain and a C2C domain. Munc13-1 was proposed to bridge synaptic vesicles to the plasma membrane in two different orientations mediated by distinct interactions of the C1C2B region with the plasma membrane: i) one involving a polybasic face that yields a perpendicular orientation of Munc13-1 and hinders release; and ii) another involving the DAG-Ca2+-PIP2-binding face that induces a slanted orientation and facilitates release. Here we have tested this model and investigated the role of the C1C2B region in neurotransmitter release. We find that K603E or R769E point mutations in the polybasic face severely impair synaptic vesicle priming in primary murine hippocampal cultures, and Ca2+-independent liposome bridging and fusion in in vitro reconstitution assays. A K720E mutation in the polybasic face and a K706E mutation in the C2B domain Ca2+-binding loops have milder effects in reconstitution assays and do not affect vesicle priming, but enhance or impair Ca2+-evoked release, respectively. The phenotypes caused by combining these mutations are dominated by the K603E and R769E mutations. Our results show that the C1-C2B region of Munc13-1 plays a central role in vesicle priming and support the notion that re-orientation of Munc13-1 controls neurotransmitter release and short-term presynaptic plasticity.

scholarly journals Short-term forms of presynaptic plasticity

2011 ◽  
Vol 21 (2) ◽  
pp. 269-274 ◽  
Author(s):  
Diasynou Fioravante ◽  
Wade G Regehr
Keyword(s):  
Short Term ◽  
Presynaptic Plasticity

scholarly journals Action potential-coupled Rho GTPase signaling drives presynaptic plasticity

2020 ◽  
Author(s):  
Shataakshi Dube ◽  
Bence Rácz ◽  
Walter E. Brown ◽  
Yudong Gao ◽  
Erik J. Soderblom ◽  
...  
Keyword(s):  
Rho Gtpase ◽  
Calcium Influx ◽  
Cell Types ◽  
Inhibitory Synapses ◽  
Fluorescence Lifetime Imaging ◽  
Short Term ◽  
Lifetime Imaging ◽  
Presynaptic Plasticity ◽  
Presynaptic Vesicle

ABSTRACTIn contrast to their postsynaptic counterparts, the contributions of activity-dependent cytoskeletal signaling to presynaptic plasticity remain controversial and poorly understood. To identify and evaluate these signaling pathways, we conducted a proteomic analysis of the presynaptic cytomatrix using in vivo biotin identification (iBioID). The resultant proteome was heavily enriched for actin cytoskeleton regulators, including Rac1, a Rho GTPase that activates the Arp2/3 complex to nucleate branched actin filaments. Strikingly, we find Rac1 and Arp2/3 are closely associated with presynaptic vesicle membranes and negatively regulate synaptic vesicle replenishment at both excitatory and inhibitory synapses. Using optogenetics and fluorescence lifetime imaging, we show this pathway bidirectionally sculpts short-term synaptic depression and that its presynaptic activation is coupled to action potentials by voltage-gated calcium influx. Thus, this study provides a new proteomic framework for understanding presynaptic physiology and uncovers a previously unrecognized mechanism of actin-regulated short-term presynaptic plasticity that is conserved across cell types.

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