Computer simulation of group Ia EPSPs using morphologically realistic models of cat alpha-motoneurons

1990 ◽  
Vol 64 (2) ◽  
pp. 648-660 ◽  
Author(s):  
I. Segev ◽  
J. W. Fleshman ◽  
R. E. Burke
Keyword(s):  
Input Resistance ◽  
The Other ◽  
Triceps Surae ◽  
Synaptic Current ◽  
Membrane Area ◽  
Synaptic Inputs ◽  
Transmembrane Voltage ◽  
Activation Times ◽  
Total Membrane ◽  
Temporal Dispersion

1. Morphological and electrophysiological data on the electrotonic structure of six triceps surae alpha-motoneurons and on the number and location of 202 Group Ia synapses making contact with ankle extensor motoneurons, previously obtained in this laboratory, were used to construct computer models to examine the generation of composite monosynaptic Group Ia excitatory postsynaptic potentials (EPSPs). 2. A total of 300 active synapses, each generating conductance transients based on voltage-clamp data and having activation times temporally dispersed (range approximately 1.3 ms) according to the conduction velocity profile of Group Ia-afferents, were used to generate composite EPSPs. 3. The shape indexes (foot-to-peak rise times and half widths) of simulated EPSPs matched those of experimentally observed Ia EPSPs reasonably well, although the rise times were, on average, approximately 0.25 ms longer in the simulated EPSPs. This may indicate that the effective temporal dispersion of actual Group Ia monosynaptic EPSPs is less than that the temporal asynchrony used in the simulations. 4. The peak amplitudes of simulated composite EPSPs (6-14 mV), as well as EPSPs produced by single somatic synapses (80-300 microV), were comparable to those found in experimental data. 5. Simulated EPSPs in motoneuron models with two forms of nonuniform Rm distribution ("step" increase from low values of Rm on the soma to much higher but uniform values in the dendrites, versus gradual monotonic "sigmoidal" increases from soma to distal dendrites) were similar in shape and amplitude. This prevented choosing one or the other Rm model as more "correct." 6. Transmembrane voltages at synaptic sites in motoneuron dendrites during generation of composite Ia EPSPs had peak amplitudes less than twice those of the somatic EPSP. The amount of nonlinearity during EPSP production was assessed by making the delivery of synaptic current independent of the local transmembrane voltage. This non-linearity was modest (less than 10%) during composite EPSP generation, consistent with previous experimental evidence. 7. The local voltages produced in various parts of different dendrites during composite EPSP generation depended on the number and location of active synapses and on the electrotonic structure of the particular dendrite. The results show that dendrites that project in different directions away from the motoneuron soma could, in principle, exhibit different degrees of interaction between Ia and other synaptic inputs. 8. Although produced by the same number of active synapses, the simulated composite Ia EPSPs varied over a two-fold range of peak amplitude in relation to motor-unit type, cell input resistance, and cell size (total membrane area).(ABSTRACT TRUNCATED AT 400 WORDS)

Analysis of effective synaptic currents generated by homonymous Ia afferent fibers in motoneurons of the cat

1988 ◽  
Vol 60 (6) ◽  
pp. 1946-1966 ◽  
Author(s):  
C. J. Heckman ◽  
M. D. Binder
Keyword(s):  
Steady State ◽  
Synaptic Input ◽  
Input Resistance ◽  
Firing Frequency ◽  
Medial Gastrocnemius ◽  
Synaptic Current ◽  
Synaptic Inputs ◽  
Input System ◽  
Synaptic Potentials ◽  
Ia Epsp

1. We have developed a technique to measure the total amount of current from a synaptic input system that reaches the soma of a motoneuron under steady-state conditions. We refer to this quantity as the effective synaptic current (IN) because only that fraction of the synaptic current that actually reaches the soma and initial segment of the cell affects its recruitment threshold and firing frequency. 2. The advantage of this technique for analysis of synaptic inputs in comparison to the standard measurements of synaptic potentials is apparent from Ohm's law. Steady-state synaptic potentials recorded at the soma of a cell are the product of IN and input resistance (RN), which is determined by intrinsic cellular properties such as cell size and membrane resistivity. Measuring IN avoids the confounding effect of RN on the amplitudes of synaptic potentials and thus provides a more direct assessment of the magnitude of a synaptic input. 3. Steady-state synaptic inputs were generated in cat medial gastrocnemius (MG) motoneurons by using tendon vibration to activate homonymous Ia afferents. We found that the magnitude of the Ia effective synaptic current (Ia IN) was not the same in all MG cells. Instead, Ia IN covaried with RN (r = 0.64; P less than 0.001), being about twice as large on average in motoneurons with high RN values as in those with low RN values. Ia IN was also correlated with motoneuron rheobase, afterhyperpolarization duration, and axonal conduction velocity. 4. A comparison of transient Ia EPSPs with steady-state Ia EPSPs (Ia EPSPSS) evoked in the same cells suggested that the effective synaptic current that produces the transient Ia EPSP was also greater in motoneurons with high RN values than in those with low RN values. 5. The factors responsible for the Ia IN-RN covariance are uncertain. However, our finding greater values of Ia IN in high RN motoneurons is consistent with other evidence suggesting that Ia boutons on these motoneurons have a higher probability for neurotransmitter release than those on low RN motoneurons (19). 6. The neural mechanisms underlying orderly recruitment are discussed. The effect of the Ia input is to produce an approximately twofold expansion of the differences in motoneuron recruitment thresholds that are generated by intrinsic cellular properties. It is suggested that the higher efficacy of Ia input in low-threshold motoneurons confers particular importance on this input system in the control of vernier movements (7).

scholarly journals Simulation of Dendritic CaV1.3 Channels in Cat Lumbar Motoneurons: Spatial Distribution

2005 ◽  
Vol 94 (6) ◽  
pp. 3961-3974 ◽  
Author(s):  
Sherif M. ElBasiouny ◽  
David J. Bennett ◽  
Vivian K. Mushahwar
Keyword(s):  
Spatial Distribution ◽  
Low Voltage ◽  
Dendritic Tree ◽  
Triceps Surae ◽  
Spinal Motoneurons ◽  
Functional Interaction ◽  
Intermediate Band ◽  
Synaptic Inputs ◽  
Persistent Inward Current ◽  
Adult Cat

We used computer simulations to study the dendritic spatial distribution of low voltage-activated L-type calcium (CaV1.3 type) channels, which mediate hysteretic persistent inward current (PIC) in spinal motoneurons. This study was prompted by the growing experimental evidence of the functional interactions between synaptic inputs and active conductances over the motoneuron dendritic tree. A compartmental cable model of an adult cat α-motoneuron was developed in NEURON simulation environment constituting the detailed morphology of type-identified triceps surae α-motoneuron and realistic distribution of group Ia afferent-to-motoneuron contacts. Simulations of different distributions of CaV1.3 channels were conducted and the resultant behavior was compared to experimental data. Our results suggest that CaV1.3 channels do not uniformly cover the whole motoneuron dendritic tree. Instead, their distribution is similar to that of synaptic contacts. We found that CaV1.3 channels are primarily localized to a wide intermediate band overlapping with the dendritic Ia-synaptic territory at dendritic distances of 300 to 850 μm (0.62 ± 0.21λ) from the soma in triceps surae α-motoneurons. These findings explain the functional interaction between synaptic inputs and the CaV1.3 channels over the motoneuron dendritic tree.

Physiological effects of two FMRFamide-related peptides from the crayfish Procambarus clarkii

1995 ◽  
Vol 198 (1) ◽  
pp. 109-116
Author(s):  
M Skerrett ◽  
A Peaire ◽  
P Quigley ◽  
A Mercier
Keyword(s):  
Transmitter Release ◽  
Procambarus Clarkii ◽  
Neuromuscular Junctions ◽  
Input Resistance ◽  
Physiological Effects ◽  
Synaptic Current ◽  
Extensor Muscles ◽  
Neuromuscular Systems ◽  
Dose Dependent ◽  
Measurable Change

The present study examined the effects of two recently identified neuropeptides on crayfish hearts and on neuromuscular junctions of the crayfish deep abdominal extensor muscles. The two peptides, referred to as NF1 (Asn-Arg-Asn-Phe-Leu-Arg-Phe-NH2) and DF2 (Asp-Arg-Asn-Phe-Leu-Arg-Phe-NH2), increased the rate and amplitude of spontaneous cardiac contractions and increased the amplitude of excitatory junctional potentials (EJPs) in the deep extensors. Both effects were dose-dependent, but threshold and EC50 values for the cardiac effects were at least 10 times lower than for the deep extensor effects. The heart responded equally well to three sequential applications of peptide in any given preparation, but the responses of the deep extensors appeared to decline with successive peptide applications. The results support the hypothesis that these two neuropeptides act as neurohormones to modulate the cardiac and neuromuscular systems in crayfish. Quantal synaptic current recordings from the deep extensor muscles indicate that both peptides increase the number of quanta of transmitter released from synaptic terminals. Neither peptide elicited a measurable change in the size of quantal synaptic currents. NF1 caused a small increase in muscle cell input resistance, while DF2 did not alter input resistance. These data suggest that DF2 increases EJP amplitudes primarily by increasing transmitter release, while the increase elicited by NF1 appears to involve presynaptic and postsynaptic mechanisms.

scholarly journals Computational Analysis of the Impact of Chronic Stress on Intrinsic and Synaptic Excitability in the Hippocampus

2010 ◽  
Vol 103 (6) ◽  
pp. 3070-3083 ◽  
Author(s):  
Rishikesh Narayanan ◽  
Sumantra Chattarji
Keyword(s):  
Chronic Stress ◽  
Pyramidal Neurons ◽  
Three Dimensional ◽  
Input Resistance ◽  
Synaptic Potentiation ◽  
Synaptic Inputs ◽  
Hippocampal Ca3 ◽  
Ca3 Pyramidal Neurons ◽  
Dendritic Atrophy ◽  
The Impact

Dendritic atrophy and impaired long-term synaptic potentiation (LTP) are hallmarks of chronic stress-induced plasticity in the hippocampus. It has been hypothesized that these disparate structural and physiological correlates of stress lead to hippocampal dysfunction by reducing postsynaptic dendritic surface, thereby adversely affecting the availability of synaptic inputs and suppressing LTP. Here we examine the validity of this framework using biophysical models of hippocampal CA3 pyramidal neurons. To statistically match with the experimentally observed region specificity of stress-induced atrophy, we use an algorithm to systematically prune three-dimensional reconstructions of CA3 pyramidal neurons. Using this algorithm, we build a biophysically realistic computational model to analyze the effects of stress on intrinsic and synaptic excitability. We find that stress-induced atrophy of CA3 dendrites leads to an increase in input resistance, which depends exponentially on the percentage of neuronal atrophy. This increase translates directly into higher spiking frequencies in response to both somatic current injections and synaptic inputs at various locations along the dendritic arbor. Remarkably, we also find that the dendritic regions that manifest atrophy-induced synaptic hyperexcitability are governed by the region specificity of the underlying dendritic atrophy. Coupled with experimentally observed modulation of N-methyl-d-aspartate receptor currents, such hyperexcitability could tilt the balance of plasticity mechanisms in favor of synaptic potentiation over depression. Thus paradoxically, our results suggest that stress may impair hippocampal learning and memory, not by directly inhibiting LTP, but because of stress-induced facilitation of intrinsic and synaptic excitability and the consequent imbalance in bidirectional synaptic plasticity.

Filtration by superficial and deep glomeruli of normovolemic and volume-depleted rats

1986 ◽  
Vol 250 (1) ◽  
pp. F86-F91
Author(s):  
R. V. Pinnick ◽  
V. J. Savin
Keyword(s):  
Basement Membrane ◽  
Maximum Rate ◽  
Rate Of Change ◽  
The Other ◽  
Membrane Area ◽  
Morphometric Analyses ◽  
Three Samples ◽  
Glomerular Size ◽  
Glomerular Ultrafiltration

We measured glomerular ultrafiltration coefficient (Kf) of isolated superficial (S) and deep (D) glomeruli of normovolemic and volume-depleted rats. Filtration was induced in vitro, and Kf was calculated from the maximum rate of change in glomerular size. Basement membrane area (A) for each glomerulus was estimated from morphometric analyses, and glomerular capillary hydraulic conductivity (Lp) was calculated by the formula Lp = Kf/A. Kf of S and D glomeruli of normovolemic rats were 2.98 +/- 0.98 and 4.25 +/- 0.07 nl . min-1 . mmHg-1, respectively. In hypovolemic rats, Kf of S glomeruli fell by approximately 50% to 1.52 +/- 0.14 nl . min-1 . mmHg-1 (P less than 0.001), whereas Kf of D glomeruli remained unchanged at 4.28 +/- 0.10 nl . min-1 . mmHg-1. Lp, calculated using the peripheral capillary area, averaged 1.98 +/- 0.09 and 1.98 +/- 0.06 microliter . min-1 . mmHg-1 . cm-2 in S and D glomeruli of normovolemic rats and 1.89 +/- 0.11 microliter . min-1 . mmHg-1 . cm-2 in D glomeruli of hypovolemic rats. Lp of S glomeruli of volume-depleted rats (0.90 +/- 0.03 microliter . min-1 . mmHg-1 . cm-2) was lower than in any of the other three samples. Mild hypovolemia causes the Kf of S glomeruli to decline, whereas Kf of D glomeruli remains constant. The decrease in Kf occurs without an alteration in capillary area and is most likely due to a decrease in Lp.

scholarly journals Functional properties of GABA synaptic inputs onto GABA neurons in monkey prefrontal cortex

2015 ◽  
Vol 113 (6) ◽  
pp. 1850-1861 ◽  
Author(s):  
Diana C. Rotaru ◽  
Cameron Olezene ◽  
Takeaki Miyamae ◽  
Nadezhda V. Povysheva ◽  
Aleksey V. Zaitsev ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Input Resistance ◽  
Synaptic Inputs ◽  
Gaba Neurons ◽  
Decay Times ◽  
Cortical Interneurons ◽  
Dorsolateral Prefrontal ◽  
Gaba Neuron ◽  
Fast Spiking ◽  
Monkey Prefrontal Cortex

In rodent cortex GABAA receptor (GABAAR)-mediated synapses are a significant source of input onto GABA neurons, and the properties of these inputs vary among GABA neuron subtypes that differ in molecular markers and firing patterns. Some features of cortical interneurons are different between rodents and primates, but it is not known whether inhibition of GABA neurons is prominent in the primate cortex and, if so, whether these inputs show heterogeneity across GABA neuron subtypes. We thus studied GABAAR-mediated miniature synaptic events in GABAergic interneurons in layer 3 of monkey dorsolateral prefrontal cortex (DLPFC). Interneurons were identified on the basis of their firing pattern as fast spiking (FS), regular spiking (RS), burst spiking (BS), or irregular spiking (IS). Miniature synaptic events were common in all of the recorded interneurons, and the frequency of these events was highest in FS neurons. The amplitude and kinetics of miniature inhibitory postsynaptic potentials (mIPSPs) also differed between DLPFC interneuron subtypes in a manner correlated with their input resistance and membrane time constant. FS neurons had the fastest mIPSP decay times and the strongest effects of the GABAAR modulator zolpidem, suggesting that the distinctive properties of inhibitory synaptic inputs onto FS cells are in part conferred by GABAARs containing α1 subunits. Moreover, mIPSCs differed between FS and RS interneurons in a manner consistent with the mIPSP findings. These results show that in the monkey DLPFC GABAAR-mediated synaptic inputs are prominent in layer 3 interneurons and may differentially regulate the activity of different interneuron subtypes.

scholarly journals Dendritic Excitability and Neuronal Morphology as Determinants of Synaptic Efficacy

2009 ◽  
Vol 101 (4) ◽  
pp. 1847-1866 ◽  
Author(s):  
Alexander O. Komendantov ◽  
Giorgio A. Ascoli
Keyword(s):  
Pyramidal Cell ◽  
Input Resistance ◽  
Neuronal Morphology ◽  
Synaptic Efficacy ◽  
Synaptic Inputs ◽  
Nonlinear Properties ◽  
Active Dendrites ◽  
Dendritic Excitability ◽  
Ganglion Neurons ◽  
Retinal Ganglion Neurons

The ability to trigger neuronal spiking activity is one of the most important functional characteristics of synaptic inputs and can be quantified as a measure of synaptic efficacy (SE). Using model neurons with both highly simplified and real morphological structures (from a single cylindrical dendrite to a hippocampal granule cell, CA1 pyramidal cell, spinal motoneuron, and retinal ganglion neurons) we found that SE of excitatory inputs decreases with the distance from the soma and active nonlinear properties of the dendrites can counterbalance this global effect of attenuation. This phenomenon is frequency dependent, with a more prominent gain in SE observed at lower levels of background input–output neuronal activity. In contrast, there are no significant differences in SE between passive and active dendrites under higher frequencies of background activity. The influence of the nonuniform distribution of active properties on SE is also more prominent at lower background frequencies. In models with real morphologies, the effect of active dendritic conductances becomes more dramatic and inverts the SE relationship between distal and proximal locations. In active dendrites, distal synapses have higher efficacy than that of proximal ones because of arising dendritic spiking in thin branches with high-input resistance. Lower levels of dendritic excitability can make SE independent of the distance from the soma. Although increasing dendritic excitability may boost SE of distal synapses in real neurons, it may actually reduce overall SE. The results are robust with respect to morphological variation and biophysical properties of the model neurons. The model of CA1 pyramidal cell with realistic distributions of dendritic conductances demonstrated important roles of hyperpolarization-activated (h-) current and A-type K+ current in controlling the efficacy of single synaptic inputs and overall SE differently in basal and apical dendrites.

Estimating the electrotonic structure of neurons with compartmental models

1992 ◽  
Vol 68 (4) ◽  
pp. 1438-1452 ◽  
Author(s):  
W. R. Holmes ◽  
W. Rall
Keyword(s):  
Input Resistance ◽  
Morphological Data ◽  
Unknown Parameters ◽  
Membrane Area ◽  
Time Constants ◽  
Fitting Procedure ◽  
Dendritic Membrane ◽  
Membrane Resistivity ◽  
Soma Membrane ◽  
Current Transients

1. A procedure based on compartmental modeling called the "constrained inverse computation" was developed for estimating the electrotonic structure of neurons. With the constrained inverse computation, a set of N electrotonic parameters are estimated iteratively with use of a Newton-Raphson algorithm given values of N parameters that can be measured or estimated from experimental data. 2. The constrained inverse computation is illustrated by several applications to the basic example of a neuron represented as one cylinder coupled to a soma. The number of unknown parameters estimated was different (ranging from 2 to 6) when different sets of constraints were chosen. The unknowns were chosen from the following: dendritic membrane resistivity Rmd, soma membrane resistivity Rms, intracellular resistivity Ri, membrane capacity Cm, dendritic membrane area AD, soma membrane area As, electrotonic length L, and resistivity-free length, rfl (rfl = 2l/d1/2 where l and d are length and diameter of the cylinder). The values of the unknown parameters were estimated from the values of an equal number of known parameters, which were chosen from the following: the time constants and coefficients of a voltage transient tau 0, tau 1, ..., C0, C1, ..., voltage-clamp time constants tau vc1, tau vc2, ..., and input resistance RN. Note that initially, morphological data were treated as unknown, rather than known. 3. When complete morphology was not known, parameters from voltage and current transients, combined with the input resistance were not sufficient to completely specify the electrotonic structure of the neuron. For a neuron represented as a cylinder coupled to a soma, there were an infinite number of combinations of Rmd, Rms, Ri, Cm, AS, AD, and L that could be fitted to the same voltage and current transients and input resistance. 4. One reason for the nonuniqueness when complete morphology was not specified is that the Ri estimate is intrinsically bound to the morphology. Ri enters the inverse computation only in the calculation of the electrotonic length of a compartment. The electrotonic length of a compartment is l[4 Ri/(dRmd)]1/2, where l and d are the length and diameter of the compartment. Without complete morphology, the inverse computation cannot distinguish between a change in d or l and a change in Ri. Even when morphology is known, the accuracy of the Ri estimate obtained by any fitting procedure is affected by systematic errors in length and diameter measurements (i.e., tissue shrinkage); the Ri estimate is inversely proportional to the length measurement and proportional to the square root of the diameter measurement.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals A quantitative model of traffic between plasma membrane and secondary lysosomes: evaluation of inflow, lateral diffusion, and degradation.

1988 ◽  
Vol 107 (6) ◽  
pp. 2109-2115 ◽  
Author(s):  
J P Draye ◽  
P J Courtoy ◽  
J Quintart ◽  
P Baudhuin
Keyword(s):  
Plasma Membrane ◽  
Half Life ◽  
Plasma Membranes ◽  
Lateral Diffusion ◽  
Quantitative Model ◽  
Lysosomal Membrane ◽  
Membrane Area ◽  
Rat Fibroblasts ◽  
Secondary Lysosomes ◽  
Total Membrane

We present here a mathematical model that accounts for the various proportions of plasma membrane constituents occurring in the lysosomal membrane of rat fibroblasts (Draye, J.-P., J. Quintart, P. J. Courtoy, and P. Baudhuin. 1987. Eur. J. Biochem. 170: 395-403; Draye, J.-P., P. J. Courtoy, J. Quintart, and P. Baudhuin. 1987. Eur. J. Biochem. 170:405-411). It is based on contents of plasma membrane markers in purified lysosomal preparations, evaluations of their half-life in lysosomes and measurements of areas of lysosomal and plasma membranes by morphometry. In rat fibroblasts, structures labeled by a 2-h uptake of horseradish peroxidase followed by a 16-h chase (i.e., lysosomes) occupy 3% of the cellular volume and their total membrane area corresponds to 30% of the pericellular membrane area. Based on the latter values, the model predicts the rate of inflow and outflow of plasma membrane constituents into lysosomal membrane, provided their rate of degradation is known. Of the bulk of polypeptides iodinated at the cell surface, only 4% reach the lysosomes every hour, where the major part (integral of 83%) is degraded with a half-life in lysosomes of integral to 0.8 h. For specific plasma membrane constituents, this model can further account for differences in the association to the lysosomal membrane by variations in the rate either of lysosomal degradation, of inflow along the pathway from the pericellular membrane to the lysosomes, or of lateral diffusion.

Opening Ratio Effect on Electrowetting Droplet Actuation on Perforated Membranes

2009 ◽  
Author(s):  
Yuejun Zhao ◽  
Sung Kwon Cho
Keyword(s):  
Power Consumption ◽  
Sampling Method ◽  
Critical Issue ◽  
Membrane Area ◽  
Ratio Effect ◽  
Lower Power ◽  
Analytical Results ◽  
Hole Area ◽  
Opening Ratio ◽  
Total Membrane

We have previously developed a microparticle sampling method in which electrowetting-actuated droplets sweep and pick up microparticles trapped on a perforated membrane. In this configuration, a critical issue is to increase the opening ratio (ratio of opening hole area to the total membrane area) in the perforated membrane as much as possible since the higher the opening ratio the lower power consumption in the process of air suction. In contrast, increasing the opening ratio hampers successful electrowetting operations of droplets and thus sampling of microparticles. In this study, we analytically investigate effects of the opening ratio on electrowetting operations. In particular, we are looking at the reversibility of electrowetting operation. Then, we fabricate testing devices to verify the analytical results in the range of the opening ratio up to about 90%. We will also discuss detailed challenging issues in microfabrication to reach such a high opening ratio.

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