scholarly journals A dual role for α-synuclein in facilitation and depression of dopamine release from substantia nigra neurons in vivo

2020 ◽  
Vol 117 (51) ◽  
pp. 32701-32710
Author(s):  
Mahalakshmi Somayaji ◽  
Stefano Cataldi ◽  
Se Joon Choi ◽  
Robert H. Edwards ◽  
Eugene V. Mosharov ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Action Potential ◽  
Synaptic Vesicle ◽  
Neuronal Activity ◽  
Dopamine Release ◽  
Short Intervals ◽  
Presynaptic Plasticity ◽  
Presynaptic Calcium ◽  
Synaptic Vesicle Fusion

α-Synuclein is expressed at high levels at presynaptic terminals, but defining its role in the regulation of neurotransmission under physiologically relevant conditions has proven elusive. We report that, in vivo, α-synuclein is responsible for the facilitation of dopamine release triggered by action potential bursts separated by short intervals (seconds) and a depression of release with longer intervals between bursts (minutes). These forms of presynaptic plasticity appear to be independent of the presence of β- and γ-synucleins or effects on presynaptic calcium and are consistent with a role for synucleins in the enhancement of synaptic vesicle fusion and turnover. These results indicate that the presynaptic effects of α-synuclein depend on specific patterns of neuronal activity.

scholarly journals α-Synuclein facilitates dopamine release during burst firing of substantia nigra neurons in vivo

2020 ◽  
Author(s):  
Mahalakshmi Somayaji ◽  
Stefano Cataldi ◽  
Robert H. Edwards ◽  
Eugene V. Mosharov ◽  
David Sulzer
Keyword(s):  
Substantia Nigra ◽  
Action Potential ◽  
Synaptic Vesicle ◽  
Neuronal Activity ◽  
Dopamine Release ◽  
Vesicle Fusion ◽  
Burst Firing ◽  
Presynaptic Calcium ◽  
Synaptic Vesicle Fusion

Abstractα-Synuclein is expressed at high levels at presynaptic terminals, but defining its role on neurotransmission under physiologically-relevant conditions has proven elusive. We report that α-synuclein is responsible for a rapid facilitation of dopamine release during action potential bursts in vivo. This occurs in tandem with a far slower stimulus-dependent depression, appears to be independent of the presence of β- and γ-synucleins or effects on presynaptic calcium and is consistent with a role for synucleins in the enhancement of synaptic vesicle fusion and turnover. The results indicate that the presynaptic effects of α-synuclein are dependent on specific patterns of neuronal activity.

scholarly journals Action Potential Code And Cocaine Modulates Dopamine Release In Mice Striatum in vivo

2009 ◽  
Vol 96 (3) ◽  
pp. 98a
Author(s):  
P.L. Zuo ◽  
X.J. Kang ◽  
J. Fan ◽  
Q. Lei ◽  
S.R. Wang ◽  
...  
Keyword(s):  
Action Potential ◽  
Dopamine Release

In vivo characterization of somatodendritic dopamine release in the substantia nigra of 6-hydroxydopamine-lesioned rats

2004 ◽  
Vol 90 (1) ◽  
pp. 29-39 ◽  
Author(s):  
Sophie Sarre ◽  
Hong Yuan ◽  
Nadine Jonkers ◽  
An Van Hemelrijck ◽  
Guy Ebinger ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Dopamine Release ◽  
6 Hydroxydopamine ◽  
In Vivo Characterization

scholarly journals Alpha-Synuclein and Calpains Disrupt SNARE-Mediated Synaptic Vesicle Fusion During Manganese Exposure in SH-SY5Y Cells

Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 258 ◽  
Author(s):  
Can Wang ◽  
Zhuo Ma ◽  
Dong-Ying Yan ◽  
Chang Liu ◽  
Yu Deng ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Vesicle Fusion ◽  
Alpha Synuclein ◽  
Convincing Evidence ◽  
Snare Complex ◽  
Attachment Protein ◽  
Over Expression ◽  
Synaptic Vesicle Fusion

Synaptic vesicle fusion is mediated by an assembly of soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptors (SNAREs), composed of syntaxin 1, soluble NSF-attachment protein (SNAP)-25, and synaptobrevin-2/VAMP-2. Previous studies have suggested that over-exposure to manganese (Mn) could disrupt synaptic vesicle fusion by influencing SNARE complex formation, both in vitro and in vivo. However, the mechanisms underlying this effect remain unclear. Here we employed calpeptin, an inhibitor of calpains, along with a lentivirus vector containing alpha-synuclein (α-Syn) shRNA, to examine whether specific SNAP-25 cleavage and the over-expression of α-Syn disturbed the formation of the SNARE complex in SH-SY5Y cells. After cells were treated with Mn for 24 h, fragments of SNAP-25-N-terminal protein began to appear; however, this effect was reduced in the group of cells which were pre-treated with calpeptin. FM1-43-labeled synaptic vesicle fusion decreased with Mn treatment, which was consistent with the formation of SNARE complexes. The interaction of VAMP-2 and α-Syn increased significantly in normal cells in response to 100 μM Mn treatment, but decreased in LV-α-Syn shRNA cells treated with 100 μM Mn; similar results were observed in terms of the formation of SNARE complexes and FM1-43-labeled synaptic vesicle fusion. Our data suggested that Mn treatment could increase [Ca2+]i, leading to abnormally excessive calpains activity, which disrupted the SNARE complex by cleaving SNAP-25. Our data also provided convincing evidence that Mn could induce the over-expression of α-Syn; when combined with VAMP-2, α-Syn prevented VAMP-2 from joining the SNARE complex cycle.

scholarly journals Synaptic vesicle fusion along axons is driven by myelination and subsequently accelerates sheath growth in an activity-regulated manner

2020 ◽  
Author(s):  
Rafael G Almeida ◽  
Jill M Williamson ◽  
Megan E Madden ◽  
Jason J Early ◽  
Matthew G Voas ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Neuronal Activity ◽  
Vesicle Fusion ◽  
Study Activity ◽  
Synaptic Vesicle Fusion

To study activity-regulated myelination, we imaged synaptic vesicle fusion along single axons in living zebrafish, and found, surprisingly, that axonal synaptic vesicle fusion is driven by myelination. This myelin-induced axonal vesicle fusion was enriched along the unmyelinated domains into which newly-formed sheaths grew, and was promoted by neuronal activity, which in turn accelerated sheath growth. Our results indicate that neuronal activity consolidates sheath growth along axons already selected for myelination.

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 Action potential and calcium dependence of tonic somatodendritic dopamine release in the Substantia Nigra pars compacta

2018 ◽  
Vol 148 (4) ◽  
pp. 462-479 ◽  
Author(s):  
Andrew G. Yee ◽  
Blaze Forbes ◽  
Pang-Ying Cheung ◽  
Alessandro Martini ◽  
Mark H. Burrell ◽  
...  
Keyword(s):  
Substantia Nigra ◽  
Action Potential ◽  
Dopamine Release ◽  
Substantia Nigra Pars Compacta ◽  
Calcium Dependence
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