scholarly journals Calcium-Dependent Synaptic Vesicle Trafficking Underlies Indefatigable Release at the Hair Cell Afferent Fiber Synapse

Neuron ◽  
2011 ◽  
Vol 70 (2) ◽  
pp. 326-338 ◽  
Author(s):  
Michael E. Schnee ◽  
Joseph Santos-Sacchi ◽  
Manuel Castellano-Muñoz ◽  
Jee-Hyun Kong ◽  
Anthony J. Ricci
Keyword(s):  
Hair Cell ◽  
Synaptic Vesicle ◽  
Vesicle Trafficking ◽  
Afferent Fiber ◽  
Calcium Dependent

Afferent Synaptic Transmission in a Hair Cell Organ: Pharmacological and Physiological Analysis of the Role of the Extended Refractory Period

2004 ◽  
Vol 92 (2) ◽  
pp. 1105-1115 ◽  
Author(s):  
Rosie Dawkins ◽  
William F. Sewell
Keyword(s):  
Action Potential ◽  
Hair Cell ◽  
Refractory Period ◽  
Afferent Fiber ◽  
Synaptic Activity ◽  
Calcium Dependent ◽  
Voltage Dependent ◽  
Physiological Analysis ◽  
Afferent Discharge

One feature of neuronal discharge proposed to play a role in coding temporal information is the relative refractory period that follows each action potential. In neurons innervating hair cells, there is an extended refractory period that can last ≤100 ms. We have taken a pharmacological approach to examine the extended refractory period in the Xenopus lateral line organ. We show that each action potential in the afferent fiber, whether generated spontaneously or through an antidromic electrical pulse, decreases the probability of subsequent afferent discharge for a period of ≤100 ms. We show that the extended refractory period can be modulated with drugs that alter glutamatergic transmission between the hair cell and the afferent fiber. The extended refractory period can be enhanced by perfusion with agents that reduce synaptic activity. These agents include blockers of voltage-dependent transmitter release, such as cobalt, as well as glutamate receptor antagonists, such as CNQX and kynurenic acid. Conversely, perfusion with agents that increase synaptic activity through activation of the glutamate receptors, such as AMPA or kainate, reduces the magnitude of suppression during the extended refractory period. The extended refractory period is greatly reduced by iberiotoxin and tetraethylammonium (TEA), indicating it may be mediated in large part by a calcium-dependent potassium channel. The ability to modulate the extended refractory period with changes in synaptic input suggests a simple, dynamic mechanism by which strong input (i.e., large or frequent excitatory postsynaptic potentials) can be strengthened and weak inputs weakened.

scholarly journals Synaptic vesicle dynamics in mouse rod bipolar cells

2008 ◽  
Vol 25 (4) ◽  
pp. 523-533 ◽  
Author(s):  
QUN-FANG WAN ◽  
ALEJANDRO VILA ◽  
ZHEN-YU ZHOU ◽  
RUTH HEIDELBERGER
Keyword(s):  
Synaptic Vesicle ◽  
Time Constant ◽  
Active Zone ◽  
Bipolar Cell ◽  
Visual Information ◽  
Membrane Surface ◽  
Bipolar Cells ◽  
Calcium Dependent ◽  
Vesicle Dynamics ◽  
Rod Bipolar Cells

AbstractTo better understand synaptic signaling at the mammalian rod bipolar cell terminal and pave the way for applying genetic approaches to the study of visual information processing in the mammalian retina, synaptic vesicle dynamics and intraterminal calcium were monitored in terminals of acutely isolated mouse rod bipolar cells and the number of ribbon-style active zones quantified. We identified a releasable pool, corresponding to a maximum of ≈35 vesicles/ribbon-style active zone. Following depletion, this pool was refilled with a time constant of ≈7 s. The presence of a smaller, rapidly releasing pool and a small, fast component of refilling was also suggested. Following calcium channel closure, membrane surface area was restored to baseline with a time constant that ranged from 2 to 21 s depending on the magnitude of the preceding Ca2+ transient. In addition, a brief, calcium-dependent delay often preceded the start of onset of membrane recovery. Thus, several aspects of synaptic vesicle dynamics appear to be conserved between rod-dominant bipolar cells of fish and mammalian rod bipolar cells. A major difference is that the number of vesicles available for release is significantly smaller in the mouse rod bipolar cell, both as a function of the total number per neuron and on a per active zone basis.

Recent Breakthroughs in Neurotransmitter Release: Paradigm for Regulated Exocytosis?

Physiology ◽  
1995 ◽  
Vol 10 (1) ◽  
pp. 42-46
Author(s):  
G Thiel
Keyword(s):  
Synaptic Vesicle ◽  
Brain Function ◽  
Neurotransmitter Release ◽  
Synaptic Vesicles ◽  
Vesicle Trafficking ◽  
Regulated Exocytosis ◽  
Intracellular Vesicle ◽  
Vesicle Cycle ◽  
Synaptic Vesicle Cycle

Synaptic vesicles play a fundamental role in brain function by mediating the release of neurotransmitters. Neurons do not use an entirely unique secretion apparatus but rather a modification of the general secretion machinery. Moreover, the synaptic vesicle cycle has many similarities with intracellular vesicle trafficking pathways.

scholarly journals TBC1D24-TLDc-related epilepsy exercise-induced dystonia: rescue by antioxidants in a disease model

Brain ◽  
2019 ◽  
Vol 142 (8) ◽  
pp. 2319-2335 ◽  
Author(s):  
Kevin Lüthy ◽  
Davide Mei ◽  
Baptiste Fischer ◽  
Maurizio De Fusco ◽  
Jef Swerts ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Vesicle Trafficking ◽  
Disease Model ◽  
Stress Sensitivity ◽  
Compound Heterozygous ◽  
Missense Mutations ◽  
Loss Of Function ◽  
Rolandic Epilepsy ◽  
Compound Heterozygous Mutations ◽  
Exercise Induced

AbstractGenetic mutations in TBC1D24 have been associated with multiple phenotypes, with epilepsy being the main clinical manifestation. The TBC1D24 protein consists of the unique association of a Tre2/Bub2/Cdc16 (TBC) domain and a TBC/lysin motif domain/catalytic (TLDc) domain. More than 50 missense and loss-of-function mutations have been described and are spread over the entire protein. Through whole genome/exome sequencing we identified compound heterozygous mutations, R360H and G501R, within the TLDc domain, in an index family with a Rolandic epilepsy exercise-induced dystonia phenotype (http://omim.org/entry/608105). A 20-year long clinical follow-up revealed that epilepsy was self-limited in all three affected patients, but exercise-induced dystonia persisted into adulthood in two. Furthermore, we identified three additional sporadic paediatric patients with a remarkably similar phenotype, two of whom had compound heterozygous mutations consisting of an in-frame deletion I81_K84 and an A500V mutation, and the third carried T182M and G511R missense mutations, overall revealing that all six patients harbour a missense mutation in the subdomain of TLDc between residues 500 and 511. We solved the crystal structure of the conserved Drosophila TLDc domain. This allowed us to predict destabilizing effects of the G501R and G511R mutations and, to a lesser degree, of R360H and potentially A500V. Next, we characterized the functional consequences of a strong and a weak TLDc mutation (TBC1D24G501R and TBC1D24R360H) using Drosophila, where TBC1D24/Skywalker regulates synaptic vesicle trafficking. In a Drosophila model neuronally expressing human TBC1D24, we demonstrated that the TBC1D24G501R TLDc mutation causes activity-induced locomotion and synaptic vesicle trafficking defects, while TBC1D24R360H is benign. The neuronal phenotypes of the TBC1D24G501R mutation are consistent with exacerbated oxidative stress sensitivity, which is rescued by treating TBC1D24G501R mutant animals with antioxidants N-acetylcysteine amide or α-tocopherol as indicated by restored synaptic vesicle trafficking levels and sustained behavioural activity. Our data thus show that mutations in the TLDc domain of TBC1D24 cause Rolandic-type focal motor epilepsy and exercise-induced dystonia. The humanized TBC1D24G501R fly model exhibits sustained activity and vesicle transport defects. We propose that the TBC1D24/Sky TLDc domain is a reactive oxygen species sensor mediating synaptic vesicle trafficking rates that, when dysfunctional, causes a movement disorder in patients and flies. The TLDc and TBC domain mutations’ response to antioxidant treatment we observed in the animal model suggests a potential for combining antioxidant-based therapeutic approaches to TBC1D24-associated disorders with previously described lipid-altering strategies for TBC domain mutations.

scholarly journals APache Is an AP2-Interacting Protein Involved in Synaptic Vesicle Trafficking and Neuronal Development

Cell Reports ◽  
2017 ◽  
Vol 21 (12) ◽  
pp. 3596-3611 ◽  
Author(s):  
Alessandra Piccini ◽  
Enrico Castroflorio ◽  
Pierluigi Valente ◽  
Fabrizia C. Guarnieri ◽  
Davide Aprile ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Neuronal Development ◽  
Vesicle Trafficking ◽  
Interacting Protein

scholarly journals A New Kinetic Framework for Synaptic Vesicle Trafficking Tested in Synapsin Knock-Outs

2011 ◽  
Vol 31 (32) ◽  
pp. 11563-11577 ◽  
Author(s):  
T. Gabriel ◽  
E. Garcia-Perez ◽  
K. Mahfooz ◽  
J. Goni ◽  
R. Martinez-Turrillas ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Vesicle Trafficking

Levetiracetam accelerates the onset of supply rate depression in synaptic vesicle trafficking

Epilepsia ◽  
2015 ◽  
Vol 56 (4) ◽  
pp. 535-545 ◽  
Author(s):  
Elizabeth García-Pérez ◽  
Kashif Mahfooz ◽  
João Covita ◽  
Aitor Zandueta ◽  
John F. Wesseling
Keyword(s):  
Synaptic Vesicle ◽  
Vesicle Trafficking ◽  
Supply Rate
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