scholarly journals Frequency-dependent amplification of stretch-evoked excitatory input in spinal motoneurons

2012 ◽  
Vol 108 (3) ◽  
pp. 753-759 ◽  
Author(s):  
Randall K. Powers ◽  
Paul Nardelli ◽  
T. C. Cope
Keyword(s):  
Membrane Potential ◽  
Low Frequency ◽  
Excitatory Input ◽  
Medial Gastrocnemius ◽  
Frequency Dependent ◽  
Fast Kinetics ◽  
Synaptic Inputs ◽  
Slow Kinetics ◽  
Voltage Dependent ◽  
Inward Currents

Voltage-dependent calcium and sodium channels mediating persistent inward currents (PICs) amplify the effects of synaptic inputs on the membrane potential and firing rate of motoneurons. CaPIC channels are thought to be relatively slow, whereas the NaPIC channels have fast kinetics. These different characteristics influence how synaptic inputs with different frequency content are amplified; the slow kinetics of Ca channels suggest that they can only contribute to amplification of low frequency inputs (<5 Hz). To characterize frequency-dependent amplification of excitatory postsynaptic potentials (EPSPs), we measured the averaged stretch-evoked EPSPs in cat medial gastrocnemius motoneurons in decerebrate cats at different subthreshold levels of membrane potential. EPSPs were produced by muscle spindle afferents activated by stretching the homonymous and synergist muscles at frequencies of 5–50 Hz. We adjusted the stretch amplitudes at different frequencies to produce approximately the same peak-to-peak EPSP amplitude and quantified the amount of amplification by expressing the EPSP integral at different levels of depolarization as a percentage of that measured with the membrane hyperpolarized. Amplification was observed at all stretch frequencies but generally decreased with increasing stretch frequency. However, in many cells the amount of amplification was greater at 10 Hz than at 5 Hz. Fast amplification was generally reduced or absent when the lidocaine derivative QX-314 was included in the electrode solution, supporting a strong contribution from Na channels. These results suggest that NaPICs can combine with CaPICs to enhance motoneuron responses to modulations of synaptic drive over a physiologically significant range of frequencies.

Computer simulations of the effects of different synaptic input systems on motor unit recruitment

1993 ◽  
Vol 70 (5) ◽  
pp. 1827-1840 ◽  
Author(s):  
C. J. Heckman ◽  
M. D. Binder
Keyword(s):  
Motor Unit ◽  
Computer Simulations ◽  
Synaptic Input ◽  
Reciprocal Inhibition ◽  
Excitatory Input ◽  
Medial Gastrocnemius ◽  
Synaptic Inputs ◽  
Monte Carlo Techniques ◽  
Recruitment Order ◽  
Random Variance

1. The effects of four different synaptic input systems on the recruitment order within a mammalian motoneuron pool were investigated using computer simulations. The synaptic inputs and motor unit properties in the model were based as closely as possible on the available experimental data for the cat medial gastrocnemius pool and muscle. Monte Carlo techniques were employed to add random variance to the motor unit thresholds and forces and to sample the resulting recruitment orders. 2. The effects of the synaptic inputs on recruitment order depended on how they modified the range of recruitment thresholds established by differences in the intrinsic current thresholds of the motoneurons. Application of a uniform synaptic input to the pool (i.e., distributed equally to all motoneurons) resulted in a recruitment sequence that was quite stable even with the addition of large amounts of random variance. With 50% added random variance, the recruitment reversals did not exceed 8%. 3. The simulated monosynaptic input from homonymous Ia afferent fibers generated a twofold expansion of the range of recruitment thresholds beyond that attributed to the differences in the intrinsic current thresholds. The Ia input generated a small reduction in the number of recruitment reversals due to random variance (6% reversals at 50% random variance). The simulated monosynaptic vestibulospinal input generated a twofold compression of the range of recruitment thresholds that exerted a modest increase in the number of recruitment reversals (12% reversals at 50% random variance). 4. In comparison with the modest effects of the two monosynaptic inputs, the simulated oligosynpatic rubrospinal excitatory input exerted a nine-fold compression in the recruitment threshold range that resulted in a recruitment sequence that was highly sensitive to random variance. With 50% added random variance, the sequence became nearly random (40% reversals). 5. Reciprocal Ia inhibition was simulated by a uniform distribution within the pool, but its effects on recruitment order were highly dependent on the distribution of the excitatory input. Reciprocal inhibition exerted only minor effects on recruitment order when combined with the Ia or vestibulospinal inputs. However, when the excitatory drive was supplied by the rubrospinal input, even small amounts of reciprocal inhibition were sufficient to completely reverse the normal recruitment sequence. 6. The simulated monosynaptic Ia input was highly effective in compensating for the disruptive effects of rubrospinal excitation on recruitment order. Even a small Ia bias combined with the rubrospinal excitation was sufficient to halve the effects of random variance and to restore the normal recruitment sequence in the presence of rather large amounts of reciprocal inhibition.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Multiple Serotonin-Activated Currents in Isolated, Neuronal Somata from Locust Thoracic Ganglia

1992 ◽  
Vol 165 (1) ◽  
pp. 43-60 ◽  
Author(s):  
ISABEL BERMUDEZ ◽  
DAVID J. BEADLE ◽  
JACK A. BENSON
Keyword(s):  
Membrane Potential ◽  
Potassium Conductance ◽  
Membrane Conductance ◽  
Membrane Potentials ◽  
Potential Range ◽  
Neuronal Somata ◽  
Sodium Permeability ◽  
Fast Kinetics ◽  
Thoracic Ganglia ◽  
Slow Kinetics

1. Three different responses were evoked by pressure micro-application of serotonin onto freshly dissociated, current- and voltage-clamped neuronal somata from the thoracic ganglia of the locust Locusta migratoria. 2. In some neurones, an inward current, I(5HT)K, resulting from a decrease in potassium conductance, with slow kinetics and maximum activation at membrane potentials of −60 to - 70 mV, was evoked by serotonin and by the 5-HT3 agonist 2-methyl serotonin. This current was completely abolished by either 10 mmoll−1 caesium or 5 mmoll−1 rubidium and partially blocked by 50 mmoll−1 tetraethylammonium or 5 mmoll−1 4-aminopyridine. The response was antagonised by the 5-HT2-specific compounds, ketanserin and ritanserin. 3. In other somata, serotonin, 2-methyl serotonin and the 5-HT3 antagonist ICS205 930 evoked a second current, I(5HT)Na, which was due to an increase in sodium permeability and had slow kinetics similar to that of I(5HT)K. This current was inward over the membrane potential range −30 to - 80 mV and increased with hyperpolarisation. The response was blocked by sodium-free saline and the 5-HT3 receptor antagonist MDL 72222. 4. In other neurones, at membrane potentials more positive than - 50 mV, serotonin pulses could activate a third current, I(5HT)X, which increased with depolarisation of the membrane potential and had comparatively fast kinetics. Activation of the current was accompanied by a decrease in membrane conductance. This response was completely blocked by 4-aminopyridine and weakly inhibited by both caesium and tetraethylammonium and is, therefore, probably a potassium current. 5. The three currents described here differ in their pharmacology, their ionic mechanisms and their dependence on membrane potential from the serotoninactivated currents reported for vertebrates and they provide evidence for the mechanism of action of serotonin as a neurotransmitter in insects. Note: Present address: Pharmacology Institute, University of Zurich, Gloriastrasse 32, CH-8006 Zurich, Switzerland.

Fast Amplification of Dynamic Synaptic Inputs in Spinal Motoneurons In Vivo

2006 ◽  
Vol 96 (5) ◽  
pp. 2200-2206 ◽  
Author(s):  
Sarah M. Jones ◽  
Robert H. Lee
Keyword(s):  
High Frequency ◽  
Tendon Vibration ◽  
Spinal Motoneurons ◽  
Synaptic Inputs ◽  
State Response ◽  
Voltage Dependent ◽  
Inward Currents ◽  
The Difference ◽  
Adult Cat

The ability of voltage-dependent inward currents (likely Na+) of the adult cat lumbar motoneurons to amplify rapidly changing (i.e., dynamic) synaptic inputs was investigated using in vivo intracellular recording techniques. Fast amplification was assessed by measuring the magnitude of the high-frequency (180 Hz) component of the Ia synaptic input due to tendon vibration as a function of somatic voltage and was compared with the previously observed amplification of steady inputs (steady state response of PICs to slow inputs). Data from 17 experiments show that amplification of the dynamic input indeed occurred and was directly linked to neuromodulatory drive (standard state: decerebrate with intact descending neuromodulatory systems vs. minimal state: pentobarbital with said systems significantly inhibited). Fast amplification factors averaged 2.0 ± 0.7 (mean ± SD) in the standard neuromodulatory state. That is, the effective synaptic current was nearly twice as large at its peak as it was at hyperpolarized levels, ranging as high as 2.6. Although fast amplification was often smaller than the amplification of steady inputs, the difference was not statistically significant. However, the voltage at which fast amplification began was ∼10 mV more depolarized ( P < 0.01). It is concluded that both dynamic and steady inputs can be amplified, but there may be differences in mechanism.

scholarly journals Synaptic control of the shape of the motoneuron pool input-output function

2017 ◽  
Vol 117 (3) ◽  
pp. 1171-1184 ◽  
Author(s):  
Randall K. Powers ◽  
Charles J. Heckman
Keyword(s):  
Synaptic Input ◽  
Excitatory Input ◽  
Motor Output ◽  
Medial Gastrocnemius ◽  
Output Function ◽  
Input Output ◽  
Synaptic Inputs ◽  
Motoneuron Pool ◽  
Synaptic Control ◽  
Excitatory Drive

Although motoneurons have often been considered to be fairly linear transducers of synaptic input, recent evidence suggests that strong persistent inward currents (PICs) in motoneurons allow neuromodulatory and inhibitory synaptic inputs to induce large nonlinearities in the relation between the level of excitatory input and motor output. To try to estimate the possible extent of this nonlinearity, we developed a pool of model motoneurons designed to replicate the characteristics of motoneuron input-output properties measured in medial gastrocnemius motoneurons in the decerebrate cat with voltage-clamp and current-clamp techniques. We drove the model pool with a range of synaptic inputs consisting of various mixtures of excitation, inhibition, and neuromodulation. We then looked at the relation between excitatory drive and total pool output. Our results revealed that the PICs not only enhance gain but also induce a strong nonlinearity in the relation between the average firing rate of the motoneuron pool and the level of excitatory input. The relation between the total simulated force output and input was somewhat more linear because of higher force outputs in later-recruited units. We also found that the nonlinearity can be increased by increasing neuromodulatory input and/or balanced inhibitory input and minimized by a reciprocal, push-pull pattern of inhibition. We consider the possibility that a flexible input-output function may allow motor output to be tuned to match the widely varying demands of the normal motor repertoire. NEW & NOTEWORTHY Motoneuron activity is generally considered to reflect the level of excitatory drive. However, the activation of voltage-dependent intrinsic conductances can distort the relation between excitatory drive and the total output of a pool of motoneurons. Using a pool of realistic motoneuron models, we show that pool output can be a highly nonlinear function of synaptic input but linearity can be achieved through adjusting the time course of excitatory and inhibitory synaptic inputs.

Intracellular analysis of excitatory-inhibitory synaptic interactions in crayfish stretch receptors

1991 ◽  
Vol 66 (3) ◽  
pp. 894-904 ◽  
Author(s):  
L. C. Barrio ◽  
A. Araque ◽  
V. Abraira ◽  
W. Buno
Keyword(s):  
Membrane Potential ◽  
Firing Rate ◽  
Discharge Rate ◽  
Low Frequency ◽  
Excitatory Input ◽  
Membrane Properties ◽  
Special Effects ◽  
Stretch Receptors ◽  
Discrete Values ◽  
Excitatory Drive

1. To determine the membrane mechanisms underlying the interactions between inhibitory postsynaptic potentials (IPSPs) and excitatory inputs, we investigated, at the membrane potential level, the combined influences of low-frequency (0.05-0.50 Hz) imposed sinusoidal transmembrane currents (termed sine currents), representing the excitatory drive, and trains of regular (3-30/s) IPSPs. The two simplest possible neuron systems exemplified by the slowly and rapidly adapting stretch receptors of crayfish (RM1 and RM2, respectively) were used. 2. At constant elongation the RM1 and RM2 behaved as a pacemaker and a neuron without self-sustained oscillations, respectively, but in dynamic conditions uninhibited controls and IPSP sine current interactions were essentially identical in both RMs. Controls showed the usual smooth variation of the RM firing rate in response to the gradually varying excitatory input. IPSP effects were characterized by the expected overall reduction of the postsynaptic firing rate. More important, special effects were also present, such as the simple fixed alternations of IPSP and postsynaptic spikes (e.g., 1 IPSP, 1 postsynaptic or 1:1; 1 IPSP, 2 postsynaptic or 1:2; 2 IPSPs, 1 postsynaptic spike or 2:1), where interspike intervals were more constant than uninhibited controls and where the sensitivity to the excitatory input was reduced to small values, and the sudden firing rate discontinuities consisting of instantaneous discharge accelerations or decelerations (termed "jumps") between successive alteration ratios, where sensitivity increased to large values. Therefore with inhibition the RM firing rate varied discontinuously in response to the gradually changing input, and the discharge rate could take one of several discrete values by switching between different alteration ratios. 3. At the alternations the times elapsed between an IPSP and the closest spike before (phase, phi) or after it (cophase, theta) increased and decreased, respectively, with increasing excitation. The major membrane potential modification that accompanied the interactions at the alternations was the gradual increase of the post-IPSP slope as a function of excitatory drive, which reduced the time to reach the firing level or theta. 4. Inhibition introduced subtle and complex nonlinear modifications in the coding of convergent excitatory input. The most notable nonlinearity was the discontinuous variations of the firing rate as a function of the gradually changing excitatory input. Effects were due to voltage interactions occurring at the extrasynaptic membrane, with a decisive involvement of the spike generator and insignificant participation of the shunting action of IPSPs. The results provide yet another example of the predominant influence of intrinsic membrane properties in determining the effects of synaptic-evoked activity.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Probing an Open CFTR Pore with Organic Anion Blockers

2002 ◽  
Vol 120 (5) ◽  
pp. 647-662 ◽  
Author(s):  
Zhen Zhou ◽  
Shenghui Hu ◽  
Tzyh-Chang Hwang
Keyword(s):  
Binding Site ◽  
Voltage Dependence ◽  
Organic Anion ◽  
Kinetic Studies ◽  
Transmembrane Conductance Regulator ◽  
Fast Kinetics ◽  
Slow Kinetics ◽  
Kd Values ◽  
Voltage Dependent ◽  
Physical And Chemical

The cystic fibrosis transmembrane conductance regulator (CFTR) is an ion channel that conducts Cl− current. We explored the CFTR pore by studying voltage-dependent blockade of the channel by two organic anions: glibenclamide and isethionate. To simplify the kinetic analysis, a CFTR mutant, K1250A-CFTR, was used because this mutant channel, once opened, can remain open for minutes. Dose–response relationships of both blockers follow a simple Michaelis-Menten function with Kd values that differ by three orders of magnitude. Glibenclamide blocks CFTR from the intracellular side of the membrane with slow kinetics. Both the on and off rates of glibenclamide block are voltage dependent. Removing external Cl− increases affinity of glibenclamide due to a decrease of the off rate and an increase of the on rate, suggesting the presence of a Cl− binding site external to the glibenclamide binding site. Isethionate blocks the channel from the cytoplasmic side with fast kinetics, but has no measurable effect when applied extracellularly. Increasing the internal Cl− concentration reduces isethionate block without affecting its voltage dependence, suggesting that Cl− and isethionate compete for a binding site in the pore. The voltage dependence and external Cl− concentration dependence of isethionate block are nearly identical to those of glibenclamide block, suggesting that these two blockers may bind to a common binding site, an idea further supported by kinetic studies of blocking with glibenclamide/isethionate mixtures. By comparing the physical and chemical natures of these two blockers, we propose that CFTR channel has an asymmetric pore with a wide internal entrance and a deeply embedded blocker binding site where local charges as well as hydrophobic components determine the affinity of the blockers.

scholarly journals Low-voltage activated (LVA) inward current in murine antral smooth muscle cells is an artifact

2021 ◽  
Author(s):  
Ji Yeon Lee ◽  
Haifeng Zheng ◽  
Kenton M. Sanders ◽  
Sang Don Koh
Keyword(s):  
Low Voltage ◽  
External Solution ◽  
Physiological Salt Solution ◽  
Channel Blockers ◽  
Free Solution ◽  
Inward Current ◽  
High K ◽  
Voltage Dependent ◽  
Inward Currents ◽  
Rich Solution

We characterized the two types of voltage-dependent inward currents in murine antral SMC. The HVA and LVA inward currents were identified when cells were bathed in Ca2+-containing physiological salt solution. We examined whether the LVA inward current was due to: 1) T-type Ca2+ channels, 2) Ca2+-activated Cl- channels, 3) non-selective cation channels (NSCC) or 4) voltage-dependent K+ channels with internal Cs+-rich solution. Replacement of external Ca2+ (2 mM) with equimolar Ba2+ increased the amplitude of the HVA current but blocked the LVA current. Nicardipine blocked the HVA current, and in the presence of nicardipine, T-type Ca2+ blockers failed to block LVA. The Cl- channel antagonist had little effect on LVA. Cation-free external solution completely abolished both HVA and LVA. Addition of Ca2+ in cation-free solution restored only HVA currents. Addition of K+ (5 mM) to cation-free solution induced LVA current that reversed at -20 mV. These data suggest that LVA is not due to T-type Ca2+ channels, Ca2+-activated Cl- channels or NSCC. Antral SMC express A-type K+ currents (KA) and delayed rectifying K+ currents (KV) with dialysis of high K+ (140 mM) solution. When cells were exposed to high K+ external solution with dialysis of Cs+-rich solution in the presence of nicardipine, LVA was evoked and reversed at positive potentials. These HK-induced inward currents were blocked by K+ channel blockers, 4-aminopyridine and TEA. In conclusion, LVA inward currents can be generated by K+ influx via KA and KV channels in murine antral SMC when cells were dialyzed with Cs+-rich solution.

Effects of ouabain on background and voltage-dependent currents in canine colonic myocytes

1990 ◽  
Vol 259 (3) ◽  
pp. C402-C408 ◽  
Author(s):  
E. P. Burke ◽  
K. M. Sanders
Keyword(s):  
Membrane Potential ◽  
Potential Gradient ◽  
Circular Muscle ◽  
Input Resistance ◽  
Pump Current ◽  
Muscle Layer ◽  
Membrane Properties ◽  
Resting Potential ◽  
Voltage Dependent ◽  
In Cells

Previous studies have suggested that the membrane potential gradient across the circular muscle layer of the canine proximal colon is due to a gradient in the contribution of the Na(+)-K(+)-ATPase. Cells at the submucosal border generate approximately 35 mV of pump potential, whereas at the myenteric border the pump contributes very little to resting potential. Results from experiments in intact muscles in which the pump is blocked are somewhat difficult to interpret because of possible effects of pump inhibitors on membrane conductances. Therefore, we studied isolated colonic myocytes to test the effects of ouabain on passive membrane properties and voltage-dependent currents. Ouabain (10(-5) M) depolarized cells and decreased input resistance from 0.487 +/- 0.060 to 0.292 +/- 0.040 G omega. The decrease in resistance was attributed to an increase in K+ conductance. Studies were also performed to measure the ouabain-dependent current. At 37 degrees C, in cells dialyzed with 19 mM intracellular Na+ concentration [( Na+]i), ouabain caused an inward current averaging 71.06 +/- 7.49 pA, which was attributed to blockade of pump current. At 24 degrees C or in cells dialyzed with low [Na+]i (11 mM), ouabain caused little change in holding current. With the input resistance of colonic cells, pump current appears capable of generating at least 35 mV. Thus an electrogenic Na+ pump could contribute significantly to membrane potential.

Preparing for the unpredictable: adaptive feedback enhances the response to unexpected communication signals

2012 ◽  
Vol 107 (4) ◽  
pp. 1241-1246 ◽  
Author(s):  
Gary Marsat ◽  
Leonard Maler
Keyword(s):  
Nervous System ◽  
Sensory Input ◽  
Low Frequency ◽  
Excitatory Input ◽  
Negative Image ◽  
Communication Signals ◽  
First Order ◽  
Communication Signal ◽  
Apical Dendrites ◽  
Spike Bursts

To interact with the environment efficiently, the nervous system must generate expectations about redundant sensory signals and detect unexpected ones. Neural circuits can, for example, compare a prediction of the sensory signal that was generated by the nervous system with the incoming sensory input, to generate a response selective to novel stimuli. In the first-order electrosensory neurons of a gymnotiform electric fish, a negative image of low-frequency redundant communication signals is subtracted from the neural response via feedback, allowing unpredictable signals to be extracted. Here we show that the cancelling feedback not only suppresses the predictable signal but also actively enhances the response to the unpredictable communication signal. A transient mismatch between the predictive feedback and incoming sensory input causes both to be positive: the soma is suddenly depolarized by the unpredictable input, whereas the neuron's apical dendrites remain depolarized by the lagging cancelling feedback. The apical dendrites allow the backpropagation of somatic spikes. We show that backpropagation is enhanced when the dendrites are depolarized, causing the unpredictable excitatory input to evoke spike bursts. As a consequence, the feedback driven by a predictable low-frequency signal not only suppresses the response to a redundant stimulus but also induces a bursting response triggered by unpredictable communication signals.

Sign in / Sign up

Export Citation Format

Share Document