scholarly journals Asynchronous glutamate exocytosis is enhanced in low release probability synapses and is widely dispersed across the active zone.

2021 ◽  
Author(s):  
Philipe Mendonca ◽  
Erica Tagliatti ◽  
Helen Langley ◽  
Dimitrios Kotzadimitriou ◽  
Criseida Zamora-Chimal ◽  
...  
Keyword(s):  
Pyramidal Cells ◽  
Network Activity ◽  
Release Probability ◽  
Synaptic Vesicle Exocytosis ◽  
Neuronal Synapses ◽  
Neuronal Network Activity ◽  
Vesicle Exocytosis ◽  
Universal Relationship ◽  
Release Area ◽  
Asynchronous Release

Abstract The balance between fast synchronous and delayed asynchronous release of neurotransmitters has a major role in defining computational properties of neuronal synapses and regulation of neuronal network activity. However, how it is tuned at the single synapse level remains poorly understood. Here, using the fluorescent glutamate sensor SF-iGluSnFR, we image quantal vesicular release in tens to hundreds of individual synaptic outputs from single pyramidal cells with 4 millisecond temporal and 75 nm spatial resolution. We find that the ratio between synchronous and asynchronous synaptic vesicle exocytosis varies extensively among synapses supplied by the same axon, and that and that synchronicity of release is reduced at low release probability synapses. We further demonstrate that asynchronous exocytosis sites are more widely distributed within the release area than synchronous sites. Together, our results reveal a universal relationship between the two major functional properties of synapses – the timing and the probability of neurotransmitter release.

scholarly journals Computer modeling of hippocampal CA1 pyramidal cells - a tool for in silico experiments

2015 ◽  
Vol 61 (1) ◽  
pp. 15-24 ◽  
Author(s):  
Júlia Metz ◽  
T. Szilágyi ◽  
M. Perian ◽  
K. Orbán-Kis
Keyword(s):  
Pyramidal Cell ◽  
In Silico ◽  
Action Potentials ◽  
Firing Pattern ◽  
Cell Model ◽  
Pyramidal Cells ◽  
Spike Timing ◽  
Network Activity ◽  
Ca1 Pyramidal Cells ◽  
Neuronal Network Activity

Abstract Objective. In silico experiments use mathematical models that capture as much as possible from the properties of the biological system under investigation. Our aim was to test the publicly available CA1 pyramidal cell models using the same simulation tasks, to compare them, and provide a systematic overview of their properties in order to improve the usefulness of these models as a tool for in silico experiments. Methods. Parameters describing the morphology of the cells and the implemented biophysical mechanisms were collected from the Model DB database of Sense Lab Project. This data was analyzed in correlation with the purpose for which each particular model was developed. Multicompartmental simulations were run using the Neuron modeling platform. The properties of the action potentials generated in response to current injection, the firing pattern and the dendritic back-propagation were analyzed. Results. The studied models were optimized to explore different physiological and pathological properties of the CA1 pyramidal cells. We could identify four broad classes of models focusing on: (i) initiation of the action potential, firing pattern and spike timing, (ii) dendritic backpropagation, (iii) dendritic integration of synaptic inputs and (iv) neuronal network activity. Despite the large variation of the active conductances implemented in the models, the properties of the individual action potentials were quite similar, but even the most complex models could not reproduce all studied biological phenomena. Conclusions. At the moment the “perfect” pyramidal cell model is not yet available. Our work, hopefully, will help finding the best model for each scientific question under investigation.

scholarly journals Liprin-α2 promotes the presynaptic recruitment and turnover of RIM1/CASK to facilitate synaptic transmission

2013 ◽  
Vol 201 (6) ◽  
pp. 915-928 ◽  
Author(s):  
Samantha A. Spangler ◽  
Sabine K. Schmitz ◽  
Josta T. Kevenaar ◽  
Esther de Graaff ◽  
Heidi de Wit ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Active Zone ◽  
Molecular Complexes ◽  
Ubiquitin Proteasome System ◽  
Synaptic Activity ◽  
Network Activity ◽  
Synaptic Vesicle Exocytosis ◽  
Vesicle Exocytosis ◽  
Ubiquitin Proteasome ◽  
Synaptic Vesicle Release

The presynaptic active zone mediates synaptic vesicle exocytosis, and modulation of its molecular composition is important for many types of synaptic plasticity. Here, we identify synaptic scaffold protein liprin-α2 as a key organizer in this process. We show that liprin-α2 levels were regulated by synaptic activity and the ubiquitin–proteasome system. Furthermore, liprin-α2 organized presynaptic ultrastructure and controlled synaptic output by regulating synaptic vesicle pool size. The presence of liprin-α2 at presynaptic sites did not depend on other active zone scaffolding proteins but was critical for recruitment of several components of the release machinery, including RIM1 and CASK. Fluorescence recovery after photobleaching showed that depletion of liprin-α2 resulted in reduced turnover of RIM1 and CASK at presynaptic terminals, suggesting that liprin-α2 promotes dynamic scaffolding for molecular complexes that facilitate synaptic vesicle release. Therefore, liprin-α2 plays an important role in maintaining active zone dynamics to modulate synaptic efficacy in response to changes in network activity.

scholarly journals Synaptic vesicles transiently dock to refill release sites

2018 ◽  
Author(s):  
Grant F Kusick ◽  
Morven Chin ◽  
Sumana Raychaudhuri ◽  
Kristina Lippmann ◽  
Kadidia P Adula ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Active Zone ◽  
Synaptic Vesicles ◽  
Electrical Field Stimulation ◽  
Dependent Manner ◽  
Single Action ◽  
Calcium Dependent ◽  
Synaptic Vesicle Exocytosis ◽  
Vesicle Exocytosis ◽  
Asynchronous Release

AbstractSynaptic vesicles fuse with the plasma membrane to release neurotransmitter following an action potential, after which new vesicles must ‘dock’ to refill vacated release sites. To capture synaptic vesicle exocytosis at cultured mouse hippocampal synapses, we induced single action potentials by electrical field stimulation then subjected neurons to high-pressure freezing to examine their morphology by electron microscopy. During synchronous release, multiple vesicles can fuse at a single active zone; this multivesicular release is augmented by increasing extracellular calcium. Fusions during synchronous release are distributed throughout the active zone, whereas fusions during asynchronous release are biased toward the center of the active zone. Immediately after stimulation, the total number of docked vesicles across all synapses decreases by ∼40%. Between 8 and 14 ms, new vesicles are recruited to the plasma membrane and fully replenish the docked pool in a calcium-dependent manner, but docking of these vesicles is transient and they either undock or fuse within 100 ms. These results demonstrate that recruitment of synaptic vesicles to release sites is rapid and reversible.

Desynchronisation of neuronal network activity in traumatic brain injury

2008 ◽  
Vol 39 (01) ◽  
Author(s):  
F Otto ◽  
J Opatz ◽  
R Hartmann ◽  
D Willbold ◽  
E Donauer ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neuronal Network ◽  
Network Activity ◽  
Neuronal Network Activity

Dementia with Lewy bodies—associated ß-synuclein mutations V70M and P123H cause mutation-specific neuropathological lesions

2021 ◽  
Author(s):  
Maryna Psol ◽  
Sofia Guerin Darvas ◽  
Kristian Leite ◽  
Sameehan U Mahajani ◽  
Mathias Bähr ◽  
...  
Keyword(s):  
Neuronal Network ◽  
Dementia With Lewy Bodies ◽  
Lewy Bodies ◽  
Sporadic Case ◽  
Network Activity ◽  
Proteinase K ◽  
Neuronal Network Activity ◽  
Distinct Disease

Abstract ß-Synuclein (ß-Syn) has long been considered to be an attenuator for the neuropathological effects caused by the Parkinson’s disease-related α-Synuclein (α-Syn) protein. However, recent studies demonstrated that overabundant ß-Syn can form aggregates and induce neurodegeneration in CNS neurons in vitro and in vivo, albeit at a slower pace as compared to α-Syn. Here we demonstrate that ß-Syn mutants V70M, detected in a sporadic case of Dementia with Lewy Bodies (DLB), and P123H, detected in a familial case of DLB, robustly aggravate the neurotoxic potential of ß-Syn. Intriguingly, the two mutations trigger mutually exclusive pathways. ß-Syn V70M enhances morphological mitochondrial deterioration and degeneration of dopaminergic and non-dopaminergic neurons, but has no influence on neuronal network activity. Conversely, ß-Syn P123H silences neuronal network activity, but does not aggravate neurodegeneration. ß-Syn WT, V70M and P123H formed proteinase K (PK) resistant intracellular fibrils within neurons, albeit with less stable C-termini as compared to α-Syn. Under cell free conditions, ß-Syn V70M demonstrated a much slower pace of fibril formation as compared to WT ß-Syn, and P123H fibrils present with a unique phenotype characterized by large numbers of short, truncated fibrils. Thus, it is possible that V70M and P123H cause structural alterations in ß-Syn, that are linked to their distinct neuropathological profiles. The extent of the lesions caused by these neuropathological profiles is almost identical to that of overabundant α-Syn, and thus likely to be directly involved into etiology of DLB. Over all, this study provides insights into distinct disease mechanisms caused by mutations of ß-Syn.

scholarly journals Neuromodulation of Astrocytic K+ Clearance

2021 ◽  
Vol 22 (5) ◽  
pp. 2520
Author(s):  
Alba Bellot-Saez ◽  
Rebecca Stevenson ◽  
Orsolya Kékesi ◽  
Evgeniia Samokhina ◽  
Yuval Ben-Abu ◽  
...  
Keyword(s):  
Oscillatory Behavior ◽  
Network Activity ◽  
Oscillatory Activity ◽  
Extracellular Potassium ◽  
Uptake Mechanism ◽  
Kir Channels ◽  
Neuronal Network Activity ◽  
Clearance Process ◽  
Spatial Buffering ◽  
The Impact

Potassium homeostasis is fundamental for brain function. Therefore, effective removal of excessive K+ from the synaptic cleft during neuronal activity is paramount. Astrocytes play a key role in K+ clearance from the extracellular milieu using various mechanisms, including uptake via Kir channels and the Na+-K+ ATPase, and spatial buffering through the astrocytic gap-junction coupled network. Recently we showed that alterations in the concentrations of extracellular potassium ([K+]o) or impairments of the astrocytic clearance mechanism affect the resonance and oscillatory behavior of both the individual and networks of neurons. These results indicate that astrocytes have the potential to modulate neuronal network activity, however, the cellular effectors that may affect the astrocytic K+ clearance process are still unknown. In this study, we have investigated the impact of neuromodulators, which are known to mediate changes in network oscillatory behavior, on the astrocytic clearance process. Our results suggest that while some neuromodulators (5-HT; NA) might affect astrocytic spatial buffering via gap-junctions, others (DA; Histamine) primarily affect the uptake mechanism via Kir channels. These results suggest that neuromodulators can affect network oscillatory activity through parallel activation of both neurons and astrocytes, establishing a synergistic mechanism to maximize the synchronous network activity.

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