Alternative to Hand-Tuning Conductance-Based Models: Construction and Analysis of Databases of Model Neurons

2003 ◽  
Vol 90 (6) ◽  
pp. 3998-4015 ◽  
Author(s):  
Astrid A. Prinz ◽  
Cyrus P. Billimoria ◽  
Eve Marder
Keyword(s):  
Activity Pattern ◽  
Phase Response Curve ◽  
Model Neuron ◽  
Compartment Model ◽  
Resting Potential ◽  
Burst Frequency ◽  
Membrane Conductances ◽  
Single Compartment Model ◽  
Activity Types ◽  
Insight Into

Conventionally, the parameters of neuronal models are hand-tuned using trial-and-error searches to produce a desired behavior. Here, we present an alternative approach. We have generated a database of about 1.7 million single-compartment model neurons by independently varying 8 maximal membrane conductances based on measurements from lobster stomatogastric neurons. We classified the spontaneous electrical activity of each model neuron and its responsiveness to inputs during runtime with an adaptive algorithm and saved a reduced version of each neuron's activity pattern. Our analysis of the distribution of different activity types (silent, spiking, bursting, irregular) in the 8-dimensional conductance space indicates that the coarse grid of conductance values we chose is sufficient to capture the salient features of the distribution. The database can be searched for different combinations of neuron properties such as activity type, spike or burst frequency, resting potential, frequency–current relation, and phase-response curve. We demonstrate how the database can be screened for models that reproduce the behavior of a specific biological neuron and show that the contents of the database can give insight into the way a neuron's membrane conductances determine its activity pattern and response properties. Similar databases can be constructed to explore parameter spaces in multicompartmental models or small networks, or to examine the effects of changes in the voltage dependence of currents. In all cases, database searches can provide insight into how neuronal and network properties depend on the values of the parameters in the models.

scholarly journals Noise-induced properties of active dendrites

2021 ◽  
Vol 118 (34) ◽  
pp. e2023381118
Author(s):  
Carl van Vreeswijk ◽  
Farzada Farkhooi
Keyword(s):  
Calcium Channels ◽  
Synaptic Input ◽  
Dynamic Properties ◽  
Model Neuron ◽  
Compartment Model ◽  
Deterministic System ◽  
Active Dendrites ◽  
Single Compartment Model ◽  
Relationship Of

Dendrites play an essential role in the integration of highly fluctuating input in vivo into neurons across all nervous systems. Yet, they are often studied under conditions where inputs to dendrites are sparse. The dynamic properties of active dendrites facing in vivo–like fluctuating input thus remain elusive. In this paper, we uncover dynamics in a canonical model of a dendritic compartment with active calcium channels, receiving in vivo–like fluctuating input. In a single-compartment model of the active dendrite with fast calcium activation, we show noise-induced nonmonotonic behavior in the relationship of the membrane potential output, and mean input emerges. In contrast, noise can induce bistability in the input–output relation in the system with slowly activating calcium channels. Both phenomena are absent in a noiseless condition. Furthermore, we show that timescales of the emerging stochastic bistable dynamics extend far beyond a deterministic system due to stochastic switching between the solutions. A numerical simulation of a multicompartment model neuron shows that in the presence of in vivo–like synaptic input, the bistability uncovered in our analysis persists. Our results reveal that realistic synaptic input contributes to sustained dendritic nonlinearities, and synaptic noise is a significant component of dendritic input integration.

An approach for comparative quantification of myocardial blood flow (0-15-H2O-PET), perfusion (Tc-99m-tetrofosmin-SPECT), and metabolism (F 18-FDG-PET)

2001 ◽  
Vol 40 (05) ◽  
pp. 164-171 ◽  
Author(s):  
B. Nowak ◽  
H.-J. Kaiser ◽  
S. Block ◽  
K.-C. Koch ◽  
J. vom Dahl ◽  
...  
Keyword(s):  
Blood Flow ◽  
Myocardial Blood Flow ◽  
Fdg Pet ◽  
Model Fitting ◽  
Compartment Model ◽  
Left Ventricular ◽  
Short Axis ◽  
New Approach ◽  
Single Compartment Model ◽  
Tissue Fraction

Summary Aim: In the present study a new approach has been developed for comparative quantification of absolute myocardial blood flow (MBF), myocardial perfusion, and myocardial metabolism in short-axis slices. Methods: 42 patients with severe CAD, referred for myocardial viability diagnostics, were studied consecutively with 0-15-H2O PET (H2O-PET) (twice), Tc-99m-Tetrofosmin 5PECT (TT-SPECT) and F-18-FDG PET (FDG-PET). All dato sets were reconstructed using attenuation correction and reoriented into short axis slices. Each heart was divided into three representative slices (base, rnidventricular, apex) and 18 ROIs were defined on the FDG PET images and transferred to the corresponding H2O-PET and TT-SPECT slices. TT-SPECT and FDG-PET data were normalized to the ROI showing maximum perfusion. MBF was calculated for all left-ventricular ROIs using a single-compartment-model fitting the dynamic H2O-PET studies. Microsphere equivalent MBF (MBF_micr) was calculated by multiplying MBF and tissue-fraction, a parameter which was obtained by fitting the dynamic H2O-PET studies. To reduce influence of viability only well perfused areas (>70% TT-SPECT) were used for comparative quantification. Results: First and second mean global MBF values were 0.85 ml × min-1 × g-1 and 0.84 ml × min-1 × g1, respectively, with a repeatability coefficient of 0.30 ml ÷ min-1 × gl. After sectorization mean MBF_micr was between 0.58 ml × min1 ÷ ml"1 and 0.68 ml × min-1 × ml"1 in well perfused areas. Corresponding TT-SPECT values ranged from 83 % to 91 %, and FDG-PET values from 91 % to 103%. All procedures yielded higher values for the lateral than the septal regions. Conclusion: Comparative quantification of MBF, MBF_micr, TT-SPECT perfusion and FDG-PET metabolism can be done with the introduced method in short axis slices. The obtained values agree well with experimentally validated values of MBF and MBF_micr.

scholarly journals Mechanism-Based Model of Parasite Growth and Dihydroartemisinin Pharmacodynamics in Murine Malaria

2012 ◽  
Vol 57 (1) ◽  
pp. 508-516 ◽  
Author(s):  
Kashyap Patel ◽  
Kevin T. Batty ◽  
Brioni R. Moore ◽  
Peter L. Gibbons ◽  
Jürgen B. Bulitta ◽  
...  
Keyword(s):  
Plasmodium Berghei ◽  
Model Development ◽  
Treatment Strategies ◽  
Compartment Model ◽  
Content Type ◽  
Promising Tool ◽  
Efflux Pathway ◽  
Novel Model ◽  
Insight Into ◽  
Late Trophozoite

ABSTRACTMurine models are used to study erythrocytic stages of malaria infection, because parasite morphology and development are comparable to those in human malaria infections. Mechanism-based pharmacokinetic-pharmacodynamic (PK-PD) models for antimalarials are scarce, despite their potential to optimize antimalarial combination therapy. The aim of this study was to develop a mechanism-based growth model (MBGM) forPlasmodium bergheiand then characterize the parasiticidal effect of dihydroartemisinin (DHA) in murine malaria (MBGM-PK-PD). Stage-specific (ring, early trophozoite, late trophozoite, and schizont) parasite density data from Swiss mice inoculated withPlasmodium bergheiwere used for model development in S-ADAPT. A single dose of intraperitoneal DHA (10 to 100 mg/kg) or vehicle was administered 56 h postinoculation. The MBGM explicitly reflected all four erythrocytic stages of the 24-hourP. bergheilife cycle. Merozoite invasion of erythrocytes was described by a first-order process that declined with increasing parasitemia. An efflux pathway with subsequent return was additionally required to describe the schizont data, thus representing parasite sequestration or trapping in the microvasculature, with a return to circulation. A 1-compartment model with zero-order absorption described the PK of DHA, with an estimated clearance and distribution volume of 1.95 liters h−1and 0.851 liter, respectively. Parasite killing was described by a turnover model, with DHA inhibiting the production of physiological intermediates (IC50, 1.46 ng/ml). Overall, the MBGM-PK-PD described the rise in parasitemia, the nadir following DHA dosing, and subsequent parasite resurgence. This novel model is a promising tool for studying malaria infections, identifying the stage specificity of antimalarials, and providing insight into antimalarial treatment strategies.

Cationic membrane conductances induced by intracellularly elevated cAMP and Ca2+: measurements with ion-selective microelectrodes

1987 ◽  
Vol 65 (5) ◽  
pp. 898-903 ◽  
Author(s):  
D. Swandulla
Keyword(s):  
Membrane Surface ◽  
Input Resistance ◽  
Resting Potential ◽  
Injection Technique ◽  
Pacemaker Neurons ◽  
Membrane Conductances ◽  
Pressure Injection ◽  
Ionic Fluxes ◽  
Helix Neurons ◽  
Facilitatory Action

Adenosine 3′,5′-cyclic monophosphate (cAMP) and CaCl2 were injected by a fast and quantitative pressure injection technique into voltage-clamped, identified Helix neurons. Intracellular elevation of cAMP as well as of Ca2+ activated an inward current (IcAMP and IN). To identify the ionic fluxes during IcAMP and IN changes in [Na+]i, [K+]o, [H+]i, and [Cl−]i were measured with ion-selective microelectrodes (ISMs). Near resting potential, Na+ was the main carrier of IcAMP. K+, and less effectively Ca2+, could substitute for Na+ in carrying IcAMp. H+ and Cl− were excluded as current carriers for IcAMP by means of ISMs. Simultaneous to this action, cAMP decreased a K+ conductance. This decrease was associated with a reduction of the K+ efflux activated by long-lasting depolarizing voltage steps, as directly measured with ISMs located near the external membrane surface. The nearly compensatory increase and decrease of two membrane conductances in the same neuron left the cell input resistance unchanged despite the considerable depolarizing action of intracellularly elevated cAMP. IN was also of nonspecific nature. However, our findings indicate less selectivity for the Ca2+-activated nonspecific channels. Large cations such as choline, TEA, and Tris passed nearly as well as Na+ through the channels. Measurements with ISMs showed that [H+]i and [Cl−]i were unchanged during IN. IN was largest in bursting pacemaker neurons compared with other cells of similar size. It was found to be essential for the burst production in these cells. IcAMP, on the other hand, might be involved in the presynaptic facilitatory action of cAMP, which as yet was attributed solely to a reduction of a K+ conductance.

A single compartment model of pacemaking in dissasociated Substantia nigra neurons

2013 ◽  
Vol 35 (3) ◽  
pp. 295-316 ◽  
Author(s):  
Febe Francis ◽  
Míriam R. García ◽  
Richard H. Middleton
Keyword(s):  
Substantia Nigra ◽  
Compartment Model ◽  
Single Compartment ◽  
Single Compartment Model

scholarly journals Deep Learning in Gait Parameter Prediction for OA and TKA Patients Wearing IMU Sensors

Sensors ◽  
2020 ◽  
Vol 20 (19) ◽  
pp. 5553
Author(s):  
Mohsen Sharifi Renani ◽  
Casey A. Myers ◽  
Rohola Zandie ◽  
Mohammad H. Mahoor ◽  
Bradley S. Davidson ◽  
...  
Keyword(s):  
Inertial Measurement Unit ◽  
Measurement Unit ◽  
Gait Patterns ◽  
Movement Data ◽  
Gait Parameters ◽  
Activity Types ◽  
Spatial Parameters ◽  
Total Knee ◽  
Insight Into ◽  
Sensor Locations

Quantitative assessments of patient movement quality in osteoarthritis (OA), specifically spatiotemporal gait parameters (STGPs), can provide in-depth insight into gait patterns, activity types, and changes in mobility after total knee arthroplasty (TKA). A study was conducted to benchmark the ability of multiple deep neural network (DNN) architectures to predict 12 STGPs from inertial measurement unit (IMU) data and to identify an optimal sensor combination, which has yet to be studied for OA and TKA subjects. DNNs were trained using movement data from 29 subjects, walking at slow, normal, and fast paces and evaluated with cross-fold validation over the subjects. Optimal sensor locations were determined by comparing prediction accuracy with 15 IMU configurations (pelvis, thigh, shank, and feet). Percent error across the 12 STGPs ranged from 2.1% (stride time) to 73.7% (toe-out angle) and overall was more accurate in temporal parameters than spatial parameters. The most and least accurate sensor combinations were feet-thighs and singular pelvis, respectively. DNNs showed promising results in predicting STGPs for OA and TKA subjects based on signals from IMU sensors and overcomes the dependency on sensor locations that can hinder the design of patient monitoring systems for clinical application.

scholarly journals Tissue heterogeneity in the mouse lung: effects of elastase treatment

2004 ◽  
Vol 97 (1) ◽  
pp. 204-212 ◽  
Author(s):  
Satoru Ito ◽  
Edward P. Ingenito ◽  
Stephen P. Arold ◽  
Harikrishnan Parameswaran ◽  
Nora T. Tgavalekos ◽  
...  
Keyword(s):  
Airway Resistance ◽  
Compartment Model ◽  
Mouse Lung ◽  
Tissue Elasticity ◽  
Single Compartment Model ◽  
In Series ◽  
Four Levels ◽  
Fitting Error ◽  
Tissue Elastance ◽  
Tissue Element

We developed a network model in an attempt to characterize heterogeneity of tissue elasticity of the lung. The model includes a parallel set of pathways, each consisting of an airway resistance, an airway inertance, and a tissue element connected in series. The airway resistance, airway inertance, and the hysteresivity of the tissue elements were the same in each pathway, whereas the tissue elastance (H) followed a hyperbolic distribution between a minimum and maximum. To test the model, we measured the input impedance of the respiratory system of ventilated normal and emphysematous C57BL/6 mice in closed chest condition at four levels of positive end-expiratory pressures. Mild emphysema was developed by nebulized porcine pancreatic elastase (PPE) (30 IU/day × 6 days). Respiratory mechanics were studied 3 wk following the initial treatment. The model significantly improved the fitting error compared with a single-compartment model. The PPE treatment was associated with an increase in mean alveolar diameter and a decrease in minimum, maximum, and mean H. The coefficient of variation of H was significantly larger in emphysema (40%) than that in control (32%). These results indicate that PPE treatment resulted in increased time-constant inequalities associated with a wider distribution of H. The heterogeneity of alveolar size (diameters and area) was also larger in emphysema, suggesting that the model-based tissue elastance heterogeneity may reflect the underlying heterogeneity of the alveolar structure.

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