scholarly journals A two-step docking site model predicting different short-term synaptic plasticity patterns

2018 ◽  
Vol 150 (8) ◽  
pp. 1107-1124 ◽  
Author(s):  
Camila Pulido ◽  
Alain Marty
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Site Occupancy ◽  
Synaptic Strength ◽  
Docking Site ◽  
Short Term ◽  
Site Model ◽  
Step Model ◽  
One Step ◽  
Using Data

The strength of synaptic transmission varies during trains of presynaptic action potentials, notably because of the depletion of synaptic vesicles available for release. It has remained unclear why some synapses display depression over time, whereas others facilitate or show a facilitation and depression sequence. Here we compare the predictions of various synaptic models assuming that several docking/release sites are acting in parallel. These models show variation of docking site occupancy during trains of action potentials due to vesicular release and site replenishment, which give rise to changes in synaptic strength. To conform with recent studies, we assume an initial docking site occupancy of <1, thus permitting site occupancy to increase during action potential trains and facilitation to occur. We consider both a standard one-step model and a more elaborate model that assumes a predocked state (two-step model). Whereas the one-step model predicts monotonic changes of synaptic strength during a train, the two-step model allows nonmonotonic changes, including the often-observed facilitation/depression sequence. Both models predict a partitioning of parameter space between initially depressing and facilitating synapses. Using data obtained from interneuron synapses in the cerebellum, we demonstrate an unusual form of depression/facilitation sequence for very high release probability after prolonged depolarization-induced transmitter release. These results indicate a depletion of predocked vesicles in the two-step model. By permitting docking site occupancy to be <1 at rest, and by incorporating a separate predocked state, we reveal that docking site models can be expanded to mimic the large variety of time-dependent changes of synaptic strength that have been observed during action potential trains. Furthermore, the two-step model provides an effective framework to identify the specific mechanisms responsible for short-term changes in synaptic strength.

scholarly journals Doc2b Ca2+ binding site mutants enhance synaptic release at rest at the expense of sustained synaptic strength

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Quentin Bourgeois-Jaarsma ◽  
Matthijs Verhage ◽  
Alexander J. Groffen
Keyword(s):  
Binding Site ◽  
Neurotransmitter Release ◽  
Action Potentials ◽  
Synaptic Strength ◽  
Cultured Neurons ◽  
Loss Of Function ◽  
Short Term ◽  
Synaptic Release ◽  
Activated State ◽  
Primary Cultured Neurons

Abstract Communication between neurons involves presynaptic neurotransmitter release which can be evoked by action potentials or occur spontaneously as a result of stochastic vesicle fusion. The Ca2+-binding double C2 proteins Doc2a and –b were implicated in spontaneous and asynchronous evoked release, but the mechanism remains unclear. Here, we compared wildtype Doc2b with two Ca2+ binding site mutants named DN and 6A, previously classified as gain- and loss-of-function mutants. They carry the substitutions D218,220N or D163,218,220,303,357,359A respectively. We found that both mutants bound phospholipids at low Ca2+ concentrations and were membrane-associated in resting neurons, thus mimicking a Ca2+-activated state. Their overexpression in hippocampal primary cultured neurons had similar effects on spontaneous and evoked release, inducing high mEPSC frequencies and increased short-term depression. Together, these data suggest that the DN and 6A mutants both act as gain-of-function mutants at resting conditions.

scholarly journals Synaptic Information Transmission in a Two-State Model of Short-Term Facilitation

Entropy ◽  
2019 ◽  
Vol 21 (8) ◽  
pp. 756 ◽  
Author(s):  
Mehrdad Salmasi ◽  
Martin Stemmler ◽  
Stefan Glasauer ◽  
Alex Loebel
Keyword(s):  
Action Potential ◽  
Information Transmission ◽  
Action Potentials ◽  
Synaptic Activity ◽  
Information Rate ◽  
Short Term ◽  
Release Probability ◽  
Synaptic Facilitation ◽  
Synaptic Release ◽  
Asynchronous Release

Action potentials (spikes) can trigger the release of a neurotransmitter at chemical synapses between neurons. Such release is uncertain, as it occurs only with a certain probability. Moreover, synaptic release can occur independently of an action potential (asynchronous release) and depends on the history of synaptic activity. We focus here on short-term synaptic facilitation, in which a sequence of action potentials can temporarily increase the release probability of the synapse. In contrast to the phenomenon of short-term depression, quantifying the information transmission in facilitating synapses remains to be done. We find rigorous lower and upper bounds for the rate of information transmission in a model of synaptic facilitation. We treat the synapse as a two-state binary asymmetric channel, in which the arrival of an action potential shifts the synapse to a facilitated state, while in the absence of a spike, the synapse returns to its baseline state. The information bounds are functions of both the asynchronous and synchronous release parameters. If synchronous release facilitates more than asynchronous release, the mutual information rate increases. In contrast, short-term facilitation degrades information transmission when the synchronous release probability is intrinsically high. As synaptic release is energetically expensive, we exploit the information bounds to determine the energy–information trade-off in facilitating synapses. We show that unlike information rate, the energy-normalized information rate is robust with respect to variations in the strength of facilitation.

scholarly journals Quantitation of single action potential-evoked Ca2+ signals in CA1 pyramidal neuron presynaptic terminals

2018 ◽  
Author(s):  
Emily Church ◽  
Edaeni Hamid ◽  
Simon Alford
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Repetitive Stimulation ◽  
Short Term ◽  
C2 Domains ◽  
Single Action ◽  
Decay Times ◽  
Diffusion Rates ◽  
Spatio Temporal ◽  
Ca1 Pyramidal Neuron

AbstractPresynaptic Ca2+ evokes exocytosis, endocytosis, and short-term synaptic plasticity. However, Ca2+ flux and interactions at presynaptic molecular targets are difficult to determine, because imaging has limited resolution. We measured single varicosity presynaptic Ca2+ using Ca2+ dyes as buffers, and constructed models of Ca2+ dispersal. Action potentials evoked Ca2+ transients (peak amplitude, 789±39 nM, within 2 ms of stimulation; decay times, 119±10 ms) with little variation when measured with low-affinity dye. Endogenous Ca2+ buffering capacities, action potential-evoked free [Ca2+]¡ and total amounts entering terminals were determined using high-affinity Ca2+ dyes to buffer Ca2+ transients. These data constrained Monte Carlo (MCell) simulations of Ca2+ entry, buffering, and removal. Data were well-fit with simulations of experimentally-determined Ca2+ fluxes, buffered by simulated Calbindin28K. Simulations were consistent with clustered Ca2+ entry followed within 2 ms by diffusion throughout the varicosity. Repetitive stimulation caused free varicosity Ca2+ to sum. However, simulated in nanometer domains, its removal by pumps and buffering was negligible, while diffusion rates were high. Thus, Ca2+ within tens of nanometers of entry, did not accumulate during sequential stimuli. A model of synaptotagmin1-Ca2+ binding indicates that even with 10 μM free varicosity Ca2+, synaptogmin1 must be within tens of nanometers of channels to ensure occupation of all its Ca2+ binding sites. Repetitive stimulation, which evokes short-term synaptic enhancement, does not modify probabilities of Ca2+ fully occupying synaptotagmin1’s C2 domains, suggesting that enhancement is not mediated by Ca2+-synaptotagmin1. We conclude that at spatio-temporal scale of fusion machines, Ca2+ necessary for their activation is diffusion dominated.

scholarly journals Higher Handgrip Strength Is Linked to Better Cognitive Performance in Chinese Adults with Hypertension

2021 ◽  
Vol 11 (8) ◽  
pp. 985
Author(s):  
Shenghua Lu ◽  
Fabian Herold ◽  
Yanjie Zhang ◽  
Yuruo Lei ◽  
Arthur F. Kramer ◽  
...  
Keyword(s):  
Cognitive Performance ◽  
Short Term Memory ◽  
Handgrip Strength ◽  
Adult Health ◽  
Linear Regression Models ◽  
Chinese Adults ◽  
Short Term ◽  
Term Memory ◽  
Using Data ◽  
The Relationship

Objective: There is growing evidence that in adults, higher levels of handgrip strength (HGS) are linked to better cognitive performance. However, the relationship between HGS and cognitive performance has not been sufficiently investigated in special cohorts, such as individuals with hypertension who have an intrinsically higher risk of cognitive decline. Thus, the purpose of this study was to examine the relationship between HGS and cognitive performance in adults with hypertension using data from the Global Ageing and Adult Health Survey (SAGE). Methods: A total of 4486 Chinese adults with hypertension from the SAGE were included in this study. Absolute handgrip strength (aHGS in kilograms) was measured using a handheld electronic dynamometer, and cognitive performance was assessed in the domains of short-term memory, delayed memory, and language ability. Multiple linear regression models were fitted to examine the association between relative handgrip strength (rHGS; aHGS divided by body mass index) and measures of cognitive performance. Results: Overall, higher levels of rHGS were associated with higher scores in short-term memory (β = 0.20) and language (β = 0.63) compared with the lowest tertiles of rHGS. In male participants, higher HGS was associated with higher scores in short-term memory (β = 0.31), language (β = 0.64), and delayed memory (β = 0.22). There were no associations between rHGS and cognitive performance measures in females. Conclusion: We observed that a higher level of rHGS was associated with better cognitive performance among hypertensive male individuals. Further studies are needed to investigate the neurobiological mechanisms, including sex-specific differences driving the relationship between measures of HGS and cognitive performance in individuals with hypertension.

scholarly journals Long-Term Development of Urban Agriculture: Resilience and Sustainability of Farmers Facing the Covid-19 Pandemic in Japan

2021 ◽  
Vol 13 (8) ◽  
pp. 4316
Author(s):  
Shingo Yoshida ◽  
Hironori Yagi
Keyword(s):  
Urban Agriculture ◽  
Food Systems ◽  
Direct Marketing ◽  
Farming System ◽  
Long Term Effects ◽  
Short Term ◽  
Short Supply ◽  
Using Data ◽  
Urban People

The coronavirus disease 2019 (Covid-19) pandemic has forced global food systems to face unprecedented uncertain shocks even in terms of human health. Urban agriculture is expected to be more resilient because of its short supply chain for urban people and diversified farming activities. However, the short-and long-term effects of the Covid-19 pandemic on urban farms remain unclear. This study aims to reveal the conditions for farm resilience to the Covid-19 pandemic in 2020 and the relationship between short-term farm resilience and long-term farm development using data from a survey of 74 farms located in Tokyo. The results are as follows. First, more than half of the sample farms increased their farm sales during this period. This resilience can be called the “persistence” approach. Second, short-term farm resilience and other sustainable farm activities contributed to improving farmers’ intentions for long-term farm development and farmland preservation. Third, the most important resilience attributes were the direct marketing, entrepreneurship, and social networks of farmers. We discussed the necessity of building farmers’ transformative capabilities for a more resilient urban farming system. These results imply that support to enhance the short-term resilience of urban farms is worth more than the short-term profit of the farms.

Calcium Dynamics and Compartmentalization in Leech Neurons

2005 ◽  
Vol 94 (6) ◽  
pp. 4430-4440 ◽  
Author(s):  
Sofija Andjelic ◽  
Vincent Torre
Keyword(s):  
Information Processing ◽  
Action Potential ◽  
Action Potentials ◽  
Time Course ◽  
Ccd Camera ◽  
Calcium Dynamics ◽  
Single Action ◽  
Single Action Potential ◽  
Calcium Indicator ◽  
Mechanosensory Neurons

Calcium dynamics in leech neurons were studied using a fast CCD camera. Fluorescence changes (Δ F/ F) of the membrane impermeable calcium indicator Oregon Green were measured. The dye was pressure injected into the soma of neurons under investigation. Δ F/ F caused by a single action potential (AP) in mechanosensory neurons had approximately the same amplitude and time course in the soma and in distal processes. By contrast, in other neurons such as the Anterior Pagoda neuron, the Annulus Erector motoneuron, the L motoneuron, and other motoneurons, APs evoked by passing depolarizing current in the soma produced much larger fluorescence changes in distal processes than in the soma. When APs were evoked by stimulating one distal axon through the root, Δ F/ F was large in all distal processes but very small in the soma. Our results show a clear compartmentalization of calcium dynamics in most leech neurons in which the soma does not give propagating action potentials. In such cells, the soma, while not excitable, can affect information processing by modulating the sites of origin and conduction of AP propagation in distal excitable processes.

scholarly journals Zinc Enhances the Inhibitory Effects of Strychnine-Sensitive Glycine Receptors in Mouse Hippocampal Neurons

2007 ◽  
Vol 98 (6) ◽  
pp. 3666-3676 ◽  
Author(s):  
Hai Xia Zhang ◽  
Liu Lin Thio
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Hippocampal Neurons ◽  
Neuronal Excitability ◽  
Hippocampal Slices ◽  
Glycine Receptors ◽  
Inhibitory Effects ◽  
Action Potential Firing ◽  
Embryonic Mouse ◽  
Potential Firing

Although extracellular Zn2+ is an endogenous biphasic modulator of strychnine-sensitive glycine receptors (GlyRs), the physiological significance of this modulation remains poorly understood. Zn2+ modulation of GlyR may be especially important in the hippocampus where presynaptic Zn2+ is abundant. Using cultured embryonic mouse hippocampal neurons, we examined whether 1 μM Zn2+, a potentiating concentration, enhances the inhibitory effects of GlyRs activated by sustained glycine applications. Sustained 20 μM glycine (EC25) applications alone did not decrease the number of action potentials evoked by depolarizing steps, but they did in 1 μM Zn2+. At least part of this effect resulted from Zn2+ enhancing the GlyR-induced decrease in input resistance. Sustained 20 μM glycine applications alone did not alter neuronal bursting, a form of hyperexcitability induced by omitting extracellular Mg2+. However, sustained 20 μM glycine applications depressed neuronal bursting in 1 μM Zn2+. Zn2+ did not enhance the inhibitory effects of sustained 60 μM glycine (EC70) applications in these paradigms. These results suggest that tonic GlyR activation could decrease neuronal excitability. To test this possibility, we examined the effect of the GlyR antagonist strychnine and the Zn2+ chelator tricine on action potential firing by CA1 pyramidal neurons in mouse hippocampal slices. Co-applying strychnine and tricine slightly but significantly increased the number of action potentials fired during a depolarizing current step and decreased the rheobase for action potential firing. Thus Zn2+ may modulate neuronal excitability normally and in pathological conditions such as seizures by potentiating GlyRs tonically activated by low agonist concentrations.

Outward current and repolarization in hypoxic rat myocardium

1983 ◽  
Vol 244 (3) ◽  
pp. H341-H350
Author(s):  
C. H. Conrad ◽  
R. G. Mark ◽  
O. H. Bing
Keyword(s):  
Action Potential ◽  
Action Potentials ◽  
Outward Current ◽  
Iodoacetic Acid ◽  
Mechanical Activity ◽  
Potential Range ◽  
Papillary Muscles ◽  
Rat Myocardium ◽  
Cable Properties ◽  
Sucrose Gap

We studied the effects of brief periods (20-30 min) of hypoxia in the presence of 5 and 50 mM glucose and of glycolytic blockade (10(-4) M iodoacetic acid, IAA) on action potentials, membrane currents, and mechanical activity in rat ventricular papillary muscles using a single sucrose gap voltage-clamp technique. Steady-state outward current (iss) was determined at the end of a 500-ms clamp to the test potential following a 600-ms clamp to a holding potential of -50 mV. In the presence of 5 mM glucose, hypoxia resulted in a decrease in action potential duration (APD) and an increase in iss (on the order of 60% at 0 mV) over the potential range studied. The increase in iss did not appear to be due to an increase in leakage current or to a change in the cable properties of the preparation. Addition of 50 mM glucose prevented the change in both APD and iss with hypoxia. In addition, glycolytic blockade with IAA did not alter iss in the presence of oxygen. We conclude that an increase in iss appears to be a major factor in the abbreviation of rat ventricular action potential seen with hypoxia. Glycolysis appears to be a sufficient (with 50 mM glucose) but not necessary source of energy for the maintenance of normal iss.

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