scholarly journals A stochastic model of hippocampal synaptic plasticity with geometrical readout of enzyme dynamics

2021 ◽  
Author(s):  
Yuri Elias Rodrigues ◽  
Cezar M. Tigaret ◽  
Hélène Marie ◽  
Cian O'Donnell ◽  
Romain Veltz
Keyword(s):  
Synaptic Plasticity ◽  
Computational Models ◽  
Ex Vivo ◽  
Extracellular Fluid ◽  
Intrinsic Noise ◽  
Spike Timing ◽  
Fluid Composition ◽  
Enzyme Dynamics ◽  
Experimental Conditions

Synaptic plasticity rules used in current computational models of learning are generally insensitive to physiological factors such as spine voltage, animal age, extracellular fluid composition, and body temperature, limiting their predictive power. Here, we built a biophysically detailed synapse model inclusive of electrical dynamics, calcium-dependent signaling via CaMKII and Calcineurin (CaN) activities. The model combined multi-timescale variables, milliseconds to minutes, and intrinsic noise from stochastic ion channel gating. Analysis of the trajectories of joint CaMKII and CaN activities yielded an interpretable geometrical readout that fitted the synaptic plasticity outcomes of nine published ex vivo experiments covering various spike-timing and frequency-dependent plasticity induction protocols, animal ages, and experimental conditions. Using this new approach, we then generated maps predicting plasticity outcomes across the space of these stimulation conditions. Finally, we tested the model's robustness to in vivo-like spike time irregularity, showing that it significantly alters plasticity outcomes.

scholarly journals Dynamic modulation of spike timing-dependent calcium influx during corticostriatal upstates

2013 ◽  
Vol 110 (7) ◽  
pp. 1631-1645 ◽  
Author(s):  
R. C. Evans ◽  
Y. M. Maniar ◽  
K. T. Blackwell
Keyword(s):  
Synaptic Plasticity ◽  
Slow Wave Sleep ◽  
Calcium Influx ◽  
Spike Timing ◽  
Medium Spiny Neuron ◽  
Calcium Transients ◽  
Biophysical Model ◽  
Published Data ◽  
High Calcium

The striatum of the basal ganglia demonstrates distinctive upstate and downstate membrane potential oscillations during slow-wave sleep and under anesthetic. The upstates generate calcium transients in the dendrites, and the amplitude of these calcium transients depends strongly on the timing of the action potential (AP) within the upstate. Calcium is essential for synaptic plasticity in the striatum, and these large calcium transients during the upstates may control which synapses undergo plastic changes. To investigate the mechanisms that underlie the relationship between calcium and AP timing, we have developed a realistic biophysical model of a medium spiny neuron (MSN). We have implemented sophisticated calcium dynamics including calcium diffusion, buffering, and pump extrusion, which accurately replicate published data. Using this model, we found that either the slow inactivation of dendritic sodium channels (NaSI) or the calcium inactivation of voltage-gated calcium channels (CDI) can cause high calcium corresponding to early APs and lower calcium corresponding to later APs. We found that only CDI can account for the experimental observation that sensitivity to AP timing is dependent on NMDA receptors. Additional simulations demonstrated a mechanism by which MSNs can dynamically modulate their sensitivity to AP timing and show that sensitivity to specifically timed pre- and postsynaptic pairings (as in spike timing-dependent plasticity protocols) is altered by the timing of the pairing within the upstate. These findings have implications for synaptic plasticity in vivo during sleep when the upstate-downstate pattern is prominent in the striatum.

Exact Event-Driven Implementation for Recurrent Networks of Stochastic Perfect Integrate-and-Fire Neurons

2012 ◽  
Vol 24 (12) ◽  
pp. 3145-3180 ◽  
Author(s):  
Thibaud Taillefumier ◽  
Jonathan Touboul ◽  
Marcelo Magnasco
Keyword(s):  
Intrinsic Noise ◽  
Spike Timing ◽  
Temporal Coding ◽  
Recurrent Networks ◽  
Neural Noise ◽  
Integrate And Fire ◽  
Discretization Schemes ◽  
Event Driven ◽  
Random Variability

In vivo cortical recording reveals that indirectly driven neural assemblies can produce reliable and temporally precise spiking patterns in response to stereotyped stimulation. This suggests that despite being fundamentally noisy, the collective activity of neurons conveys information through temporal coding. Stochastic integrate-and-fire models delineate a natural theoretical framework to study the interplay of intrinsic neural noise and spike timing precision. However, there are inherent difficulties in simulating their networks’ dynamics in silico with standard numerical discretization schemes. Indeed, the well-posedness of the evolution of such networks requires temporally ordering every neuronal interaction, whereas the order of interactions is highly sensitive to the random variability of spiking times. Here, we answer these issues for perfect stochastic integrate-and-fire neurons by designing an exact event-driven algorithm for the simulation of recurrent networks, with delayed Dirac-like interactions. In addition to being exact from the mathematical standpoint, our proposed method is highly efficient numerically. We envision that our algorithm is especially indicated for studying the emergence of polychronized motifs in networks evolving under spike-timing-dependent plasticity with intrinsic noise.

Abstract 27: ApoA-I Improves Lymphatic Function Through a Platelet-Dependent Mechanism in Atherosclerotic Mice

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Andreea Milasan ◽  
François Dallaire ◽  
Gabriel Jean ◽  
Jean-Claude Tardif ◽  
Yahye Merhi ◽  
...  
Keyword(s):  
Lymphatic Vessel ◽  
Ex Vivo ◽  
Lymphatic Vessels ◽  
Lymphatic Transport ◽  
Lv Function ◽  
Experimental Conditions ◽  
Lymphatic Function ◽  
Beneficial Effects ◽  
Dependent Mechanism

Rationale: Lymphatic vessels (LVs) are now recognized as prerequisite players in the modulation of cholesterol removal from the artery wall in experimental conditions of plaque regression, and a particular attention has been brought on the role of the collecting LVs in early atherosclerosis-related lymphatic dysfunction. Whereas recent findings revealed that apoA-I restores the neovascularization capacity of the lymphatic system during tumor necrosis factor-induced inflammation, the effect of apoA-I on collecting LV function during atherosclerosis has not been tested. Objective: In the present study, we address whether and how apoA-I can enhance collecting LV function in atherosclerosis-associated lymphatic dysfunction. Methods and Results: A 6-week systemic treatment with lipid-free apoA-I enhanced lymphatic transport and abrogated collecting lymphatic vessel permeability in atherosclerotic Ldlr –/– mice when compared to control. As injection of apoA-I has been shown to protect wild-type mice against flow restriction-induced thrombosis, and that platelets are identified as key elements in the maintenance of lymphatic vessel integrity via their interaction with lymphatic endothelial cells (LECs), we have tested whether the effects of apoA-I could be mediated through a platelet-dependent mechanism. Our in vivo results show that apoA-I kinetics in lymph reflected that of blood. Ex vivo experiments performed with washed platelets isolated from mouse blood reveal that apoA-I decreased thrombin-induced but not podoplanin-induced platelet aggregation. Whereas this result suggests that apoA-I limits platelet thrombotic potential in blood but not in lymph, we demonstrate that treatment of human LECs with apoA-I increases the adhesion of bridge-like platelets on human LECs. Conclusions: Our results suggest that apoA-I can mediate beneficial effects on lymphatic function by promoting platelet adhesion to the lymphatic endothelium and consequently restore collecting LV integrity. Altogether, we bring forward a new pleiotropic role for apoA-I in lymphatic function and unveil new potential therapeutic targets for the prevention and treatment of atherosclerosis.

A New Hypothesis for Human Atherosclerotic Plaque Progression Based on Serial In Vivo MRI and Computational Modeling Method

2007 ◽  
Author(s):  
Sayan Mondal ◽  
Chun Yang ◽  
Joseph D. Petruccelli ◽  
Chun Yuan ◽  
Fei Liu ◽  
...  
Keyword(s):  
Shear Stress ◽  
Wall Thickness ◽  
Computational Models ◽  
Ex Vivo ◽  
Maximum Principal Stress ◽  
Magnetic Resonance Images ◽  
Shear Stresses ◽  
Flow Shear ◽  
Flow Shear Stress

It has been well-accepted that atherosclerosis initiation and progression correlate positively with low and oscillating flow wall shear stresses. However, this shear stress mechanism cannot fully explain why advanced plaques continue to grow under elevated flow shear stress conditions. Our previous investigations using 3D computational models with fluid-structure interactions (FSI) based on in vivo/ex vivo magnetic resonance images (MRI) of human carotid atherosclerotic plaques indicated that there is a negative correlation between advanced plaque wall thickness and structural maximum principal stress (Stress-P1) in the plaque and a positive correlation between plaque wall thickness and flow shear stress [3].

scholarly journals Models of tendon development and injury

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Sophia K. Theodossiou ◽  
Nathan R. Schiele
Keyword(s):  
Computational Models ◽  
Ex Vivo ◽  
Current Model ◽  
Stem Cell Differentiation ◽  
Tendon Injury ◽  
Model Systems ◽  
Tendon Development ◽  
Key Aspects

AbstractTendons link muscle to bone and transfer forces necessary for normal movement. Tendon injuries can be debilitating and their intrinsic healing potential is limited. These challenges have motivated the development of model systems to study the factors that regulate tendon formation and tendon injury. Recent advances in understanding of embryonic and postnatal tendon formation have inspired approaches that aimed to mimic key aspects of tendon development. Model systems have also been developed to explore factors that regulate tendon injury and healing. We highlight current model systems that explore developmentally inspired cellular, mechanical, and biochemical factors in tendon formation and tenogenic stem cell differentiation. Next, we discuss in vivo, in vitro, ex vivo, and computational models of tendon injury that examine how mechanical loading and biochemical factors contribute to tendon pathologies and healing. These tendon development and injury models show promise for identifying the factors guiding tendon formation and tendon pathologies, and will ultimately improve regenerative tissue engineering strategies and clinical outcomes.

scholarly journals Detection of the Strains Induced in Murine Tibias by Ex Vivo Uniaxial Loading with Different Sensors

Sensors ◽  
2019 ◽  
Vol 19 (23) ◽  
pp. 5109
Author(s):  
Emanuele Rizzuto ◽  
Barbara Peruzzi ◽  
Mariagrazia Giudice ◽  
Enrica Urciuoli ◽  
Erika Pittella ◽  
...  
Keyword(s):  
Standard Deviation ◽  
Ex Vivo ◽  
Mean Value ◽  
Uniaxial Loading ◽  
Image Correlation ◽  
Strain Gauges ◽  
Experimental Conditions ◽  
The Mean

In this paper, the characterization of the main techniques and transducers employed to measure local and global strains induced by uniaxial loading of murine tibiae is presented. Micro strain gauges and digital image correlation (DIC) were tested to measure local strains, while a moving coil motor-based length transducer was employed to measure relative global shortening. Local strain is the crucial parameter to be measured when dealing with bone cell mechanotransduction, so we characterized these techniques in the experimental conditions known to activate cell mechanosensing in vivo. The experimental tests were performed using tibia samples excised from twenty-two C57BL/6 mice. To evaluate measurement repeatability we computed the standard deviation of ten repetitive compressions to the mean value. This value was lower than 3% for micro strain gauges, and in the range of 7%–10% for DIC and the length transducer. The coefficient of variation, i.e., the standard deviation to the mean value, was about 35% for strain gauges and the length transducer, and about 40% for DIC. These results provided a comprehensive characterization of three methodologies for local and global bone strain measurement, suggesting a possible field of application on the basis of their advantages and limitations.

scholarly journals Rupintrivir reduces RV-induced TH-2 cytokine IL-4 in precision-cut lung slices (PCLS) of HDM-sensitized mice ex vivo

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Olga Danov ◽  
Lisa Lasswitz ◽  
Helena Obernolte ◽  
Christina Hesse ◽  
Armin Braun ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Antiviral Drug ◽  
Cytokine Response ◽  
Experimental Conditions ◽  
Tnf Α ◽  
Dust Mite ◽  
Ifn Γ ◽  
Inflammatory Immune Response ◽  
Precision Cut Lung Slices

Abstract Background Antiviral drugs such as rupintrivir may have an immune-modulatory effect in experimentally induced allergic asthma with subsequent RV infection. We infected lung slices of house-dust mite (HDM)-sensitized asthmatic mice ex vivo with human rhinovirus (RV) and investigated the effect of the antiviral drug rupintrivir on RV-induced cytokine response in lung tissue of HDM-sensitized mice ex vivo. Methods Mice were sensitized with HDM. Precision-cut lung slices (PCLS) were prepared from HDM-sensitized or non-sensitized mice. Lung slices were infected ex vivo with RV or RV together with rupintrivir. Modulation of immune responses was evaluated by cytokine secretion 48 h post infection. Results In vivo HDM sensitization resulted in a TH-2/TH-17-dominated cytokine response that persisted in PCLS ex vivo. RV infection of PCLS from non-sensitized mice resulted in the induction of an antiviral and pro-inflammatory immune response, as indicated by the secretion of IFN-α, IFN-β, IFN-γ, TNF-α, MCP-1, IP-10, IL-10, and IL-17A. In contrast, PCLS from HDM-sensitized mice showed an attenuated antiviral response, but exaggerated IL-4, IL-6, and IL-10 secretion upon infection. Rupintrivir inhibited exaggerated pro-inflammatory cytokine IL-6 and TH-2 cytokine IL-4 in HDM-sensitized mice. Conclusions In summary, this study demonstrates that treatment with rupintrivir influences virus-induced IL-4 and IL-6 cytokine release under experimental conditions ex vivo.

scholarly journals Reconciling the STDP and BCM Models of Synaptic Plasticity in a Spiking Recurrent Neural Network

2010 ◽  
Vol 22 (8) ◽  
pp. 2059-2085 ◽  
Author(s):  
Daniel Bush ◽  
Andrew Philippides ◽  
Phil Husbands ◽  
Michael O'Shea
Keyword(s):  
Neural Network ◽  
Synaptic Plasticity ◽  
Recurrent Neural Network ◽  
Hebbian Learning ◽  
Spike Timing ◽  
Synaptic Competition ◽  
Firing Rates ◽  
Plasticity Rule ◽  
Asymmetric Learning

Rate-coded Hebbian learning, as characterized by the BCM formulation, is an established computational model of synaptic plasticity. Recently it has been demonstrated that changes in the strength of synapses in vivo can also depend explicitly on the relative timing of pre- and postsynaptic firing. Computational modeling of this spike-timing-dependent plasticity (STDP) has demonstrated that it can provide inherent stability or competition based on local synaptic variables. However, it has also been demonstrated that these properties rely on synaptic weights being either depressed or unchanged by an increase in mean stochastic firing rates, which directly contradicts empirical data. Several analytical studies have addressed this apparent dichotomy and identified conditions under which distinct and disparate STDP rules can be reconciled with rate-coded Hebbian learning. The aim of this research is to verify, unify, and expand on these previous findings by manipulating each element of a standard computational STDP model in turn. This allows us to identify the conditions under which this plasticity rule can replicate experimental data obtained using both rate and temporal stimulation protocols in a spiking recurrent neural network. Our results describe how the relative scale of mean synaptic weights and their dependence on stochastic pre- or postsynaptic firing rates can be manipulated by adjusting the exact profile of the asymmetric learning window and temporal restrictions on spike pair interactions respectively. These findings imply that previously disparate models of rate-coded autoassociative learning and temporally coded heteroassociative learning, mediated by symmetric and asymmetric connections respectively, can be implemented in a single network using a single plasticity rule. However, we also demonstrate that forms of STDP that can be reconciled with rate-coded Hebbian learning do not generate inherent synaptic competition, and thus some additional mechanism is required to guarantee long-term input-output selectivity.

scholarly journals Fluid Structural Analysis of Urine Flow in a Stented Ureter

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
J. Carlos Gómez-Blanco ◽  
F. Javier Martínez-Reina ◽  
Domingo Cruz ◽  
J. Blas Pagador ◽  
Francisco M. Sánchez-Margallo ◽  
...  
Keyword(s):  
Computational Models ◽  
Mechanical Characterization ◽  
Ex Vivo ◽  
Biological Tissues ◽  
Urine Flow ◽  
Computational Environment ◽  
Computational Fluid Dynamics Cfd

Many urologists are currently studying new designs of ureteral stents to improve the quality of their operations and the subsequent recovery of the patient. In order to help during this design process, many computational models have been developed to simulate the behaviour of different biological tissues and provide a realistic computational environment to evaluate the stents. However, due to the high complexity of the involved tissues, they usually introduce simplifications to make these models less computationally demanding. In this study, the interaction between urine flow and a double-J stented ureter with a simplified geometry has been analysed. The Fluid-Structure Interaction (FSI) of urine and the ureteral wall was studied using three models for the solid domain: Mooney-Rivlin, Yeoh, and Ogden. The ureter was assumed to be quasi-incompressible and isotropic. Data obtained in previous studies from ex vivo and in vivo mechanical characterization of different ureters were used to fit the mentioned models. The results show that the interaction between the stented ureter and urine is negligible. Therefore, we can conclude that this type of models does not need to include the FSI and could be solved quite accurately assuming that the ureter is a rigid body and, thus, using the more simple Computational Fluid Dynamics (CFD) approach.

scholarly journals Modulation of Synaptic Plasticity by Glutamatergic Gliotransmission: A Modeling Study

2016 ◽  
Vol 2016 ◽  
pp. 1-30 ◽  
Author(s):  
Maurizio De Pittà ◽  
Nicolas Brunel
Keyword(s):  
Synaptic Plasticity ◽  
Glutamate Release ◽  
Spike Timing ◽  
Biophysical Model ◽  
Dependent Manner ◽  
Inward Currents ◽  
Functional Relevance ◽  
And Function ◽  
Activity Dependent

Glutamatergic gliotransmission, that is, the release of glutamate from perisynaptic astrocyte processes in an activity-dependent manner, has emerged as a potentially crucial signaling pathway for regulation of synaptic plasticity, yet its modes of expression and function in vivo remain unclear. Here, we focus on two experimentally well-identified gliotransmitter pathways, (i) modulations of synaptic release and (ii) postsynaptic slow inward currents mediated by glutamate released from astrocytes, and investigate their possible functional relevance on synaptic plasticity in a biophysical model of an astrocyte-regulated synapse. Our model predicts that both pathways could profoundly affect both short- and long-term plasticity. In particular, activity-dependent glutamate release from astrocytes could dramatically change spike-timing-dependent plasticity, turning potentiation into depression (and vice versa) for the same induction protocol.

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