THE EFFECTS OF STRYCHNINE, ESERINE, AND ACETYLCHOLINE ON THE ELECTROCORTICOGRAM AND MOTOR UNIT FIRING; TOGETHER WITH OBSERVATIONS ON THE STRETCH REFLEX IN THE MASSETER MUSCLE OF THE RABBIT

1955 ◽  
Vol 33 (1) ◽  
pp. 695-723
Author(s):  
William D. Wilkey ◽  
Frederick R. Miller

Observations were made on rabbits and cats under dial anesthesia. Monopolar recording from cortex was used. Strychnine, 1%, on motor cerebral cortex is excitatory, as shown by increased firing of motor units; later the strychnine induces cortical spikes. Each spike is triphasic, consisting of an initial, small positive wave, a large, fast negative wave, and a final, slow positive wave; the first two waves are believed to be excitomotor; the final positive wave is regarded as a positive after-potential with relative quiescence of neurons; it is not excitatory for motor units. Microwaves at high frequency occur during first positive wave and ascent of negative wave; microwaves decay during descent of negative wave and are absent during final positive wave. Microwaves are caused by fast, repetitive firing of neurons; this neuronal firing causes excitation of motor units. Intracortical and extracortical conduction are believed to be repetitive. Acetylcholine (ACh), 1%, on eserinized cortex induces triphasic spikes, resembling those from strychnine; microwaves are likewise present. Strychnine, eserine, and ACh are believed to stimulate cortical synapses. Strychnine and ACh, though very different chemically, are believed to trigger the same fundamental cortical mechanism of conduction.

1955 ◽  
Vol 33 (4) ◽  
pp. 695-723
Author(s):  
William D. Wilkey ◽  
Frederick R. Miller

Observations were made on rabbits and cats under dial anesthesia. Monopolar recording from cortex was used. Strychnine, 1%, on motor cerebral cortex is excitatory, as shown by increased firing of motor units; later the strychnine induces cortical spikes. Each spike is triphasic, consisting of an initial, small positive wave, a large, fast negative wave, and a final, slow positive wave; the first two waves are believed to be excitomotor; the final positive wave is regarded as a positive after-potential with relative quiescence of neurons; it is not excitatory for motor units. Microwaves at high frequency occur during first positive wave and ascent of negative wave; microwaves decay during descent of negative wave and are absent during final positive wave. Microwaves are caused by fast, repetitive firing of neurons; this neuronal firing causes excitation of motor units. Intracortical and extracortical conduction are believed to be repetitive. Acetylcholine (ACh), 1%, on eserinized cortex induces triphasic spikes, resembling those from strychnine; microwaves are likewise present. Strychnine, eserine, and ACh are believed to stimulate cortical synapses. Strychnine and ACh, though very different chemically, are believed to trigger the same fundamental cortical mechanism of conduction.


2002 ◽  
Vol 88 (2) ◽  
pp. 861-868 ◽  
Author(s):  
Steven D. Buckingham ◽  
Andrew N. Spencer

Certain neurons of vertebrates are specialized for high-frequency firing. Interestingly, high-frequency firing is also seen in central neurons in basal bilateral metazoans. Recently, the role of potassium currents with rightward-shifted activation curves in producing high-frequency firing has come under scrutiny. We apply intracellular recording, patch-clamp techniques, and compartmental modeling to examine the roles of rightward-shifted potassium currents in repetitive firing and shaping of action potentials in central neurons of the flatworm, Notoplana atomata ( Phylum Platyhelminthes). The kinetic properties of potassium and sodium currents were determined from patch-clamp experiments on dissociated brain cells. To predict the effects of changing the steady-state and kinetic properties of these potassium currents, these data were incorporated into a computer model of a 30-μm spherical cell with the levels of current adjusted to approximate the values recorded in voltage-clamp experiments. The model was able to support regenerative spikes at high frequencies in response to injected current. Current-clamp recordings of cultured cells and of neurons in situ also showed evidence of very-high-frequency firing. Adjusting the ratio of inactivating to non-inactivating potassium currents had little effect upon the firing pattern of the cell or its ability to fire at high frequencies, whereas the presence of the non-inactivating current was necessary for repetitive firing. Computer simulations suggested that the rightward shift in voltage sensitivity confers a raised firing threshold, while rapid channel kinetics underlie high frequency firing, and the large activation range enhances the coding range of the cell.


1987 ◽  
Vol 29 (4) ◽  
pp. 397-407 ◽  
Author(s):  
Kouichi Shiozawa ◽  
Yasutake Saeki ◽  
Keiji Yanagisawa

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chris Donnelly ◽  
Jonathan Stegmüller ◽  
Anthony J. Blazevich ◽  
Fabienne Crettaz von Roten ◽  
Bengt Kayser ◽  
...  

AbstractThe effectiveness of neuromuscular electrical stimulation (NMES) for rehabilitation is proportional to the evoked torque. The progressive increase in torque (extra torque) that may develop in response to low intensity wide-pulse high-frequency (WPHF) NMES holds great promise for rehabilitation as it overcomes the main limitation of NMES, namely discomfort. WPHF NMES extra torque is thought to result from reflexively recruited motor units at the spinal level. However, whether WPHF NMES evoked force can be modulated is unknown. Therefore, we examined the effect of two interventions known to change the state of spinal circuitry in opposite ways on evoked torque and motor unit recruitment by WPHF NMES. The interventions were high-frequency transcutaneous electrical nerve stimulation (TENS) and anodal transcutaneous spinal direct current stimulation (tsDCS). We show that TENS performed before a bout of WPHF NMES results in lower evoked torque (median change in torque time-integral: − 56%) indicating that WPHF NMES-evoked torque might be modulated. In contrast, the anodal tsDCS protocol used had no effect on any measured parameter. Our results demonstrate that WPHF NMES extra torque can be modulated and although the TENS intervention blunted extra torque production, the finding that central contribution to WPHF NMES-evoked torques can be modulated opens new avenues for designing interventions to enhance WPHF NMES.


1999 ◽  
Vol 82 (3) ◽  
pp. 1512-1528 ◽  
Author(s):  
R. Hernández-Pineda ◽  
A. Chow ◽  
Y. Amarillo ◽  
H. Moreno ◽  
M. Saganich ◽  
...  

The globus pallidus plays central roles in the basal ganglia circuitry involved in movement control as well as in cognitive and emotional functions. There is therefore great interest in the anatomic and electrophysiological characterization of this nucleus. Most pallidal neurons are GABAergic projecting cells, a large fraction of which express the calcium binding protein parvalbumin (PV). Here we show that PV-containing pallidal neurons coexpress Kv3.1 and Kv3.2 K+ channel proteins and that both Kv3.1 and Kv3.2 antibodies coprecipitate both channel proteins from pallidal membrane extracts solubilized with nondenaturing detergents, suggesting that the two channel subunits are forming heteromeric channels. Kv3.1 and Kv3.2 channels have several unusual electrophysiological properties when expressed in heterologous expression systems and are thought to play special roles in neuronal excitability including facilitating sustained high-frequency firing in fast-spiking neurons such as interneurons in the cortex and the hippocampus. Electrophysiological analysis of freshly dissociated pallidal neurons demonstrates that these cells have a current that is nearly identical to the currents expressed by Kv3.1 and Kv3.2 proteins in heterologous expression systems, including activation at very depolarized membrane potentials (more positive than −10 mV) and very fast deactivation rates. These results suggest that the electrophysiological properties of native channels containing Kv3.1 and Kv3.2 proteins in pallidal neurons are not significantly affected by factors such as associated subunits or postranslational modifications that result in channels having different properties in heterologous expression systems and native neurons. Most neurons in the globus pallidus have been reported to fire sustained trains of action potentials at high-frequency. Kv3.1–Kv3.2 voltage-gated K+channels may play a role in helping maintain sustained high-frequency repetitive firing as they probably do in other neurons.


2006 ◽  
Vol 95 (5) ◽  
pp. 3105-3112 ◽  
Author(s):  
S. Piccinin ◽  
A. D. Randall ◽  
J. T. Brown

Synchronous neuronal firing can be induced in hippocampal slices in the absence of synaptic transmission by lowering extracellular Ca2+ and raising extracellular K+. However, the ionic mechanisms underlying this nonsynaptic synchronous firing are not well understood. In this study we have investigated the role of KCNQ /Kv7 channels in regulating this form of nonsynaptic bursting activity. Incubation of rat hippocampal slices in reduced (<0.2 mM) [Ca2+]o and increased (6.3 mM) [K+]o, blocked synaptic transmission, increased neuronal firing, and led to the development of spontaneous periodic nonsynaptic epileptiform activity. This activity was recorded extracellularly as large (4.7 ± 1.9 mV) depolarizing envelopes with superimposed high-frequency synchronous population spikes. These intraburst population spikes initially occurred at a high frequency (about 120 Hz), which decayed throughout the burst stabilizing in the gamma-frequency band (30–80 Hz). Further increasing [K+]o resulted in an increase in the interburst frequency without altering the intraburst population spike frequency. Application of retigabine (10 μM), a Kv7 channel modulator, completely abolished the bursts, in an XE-991–sensitive manner. Furthermore, application of the Kv7 channel blockers, linopirdine (10 μM) or XE-991 (10 μM) alone, abolished the gamma frequency, but not the higher-frequency population spike firing observed during low Ca2+/high K+ bursts. These data suggest that Kv7 channels are likely to play a role in the regulation of synchronous population firing activity.


2018 ◽  
Vol 120 (6) ◽  
pp. 3246-3256 ◽  
Author(s):  
Spencer A. Murphy ◽  
Francesco Negro ◽  
Dario Farina ◽  
Tanya Onushko ◽  
Matthew Durand ◽  
...  

Following stroke, hyperexcitable sensory pathways, such as the group III/IV afferents that are sensitive to ischemia, may inhibit paretic motor neurons during exercise. We quantified the effects of whole leg ischemia on paretic vastus lateralis motor unit firing rates during submaximal isometric contractions. Ten chronic stroke survivors (>1 yr poststroke) and 10 controls participated. During conditions of whole leg occlusion, the discharge timings of motor units were identified from decomposition of high-density surface electromyography signals during repeated submaximal knee extensor contractions. Quadriceps resting twitch responses and near-infrared spectroscopy measurements of oxygen saturation as an indirect measure of blood flow were made. There was a greater decrease in paretic motor unit discharge rates during the occlusion compared with the controls (average decrease for stroke and controls, 12.3 ± 10.0% and 0.1 ± 12.4%, respectively; P < 0.001). The motor unit recruitment thresholds did not change with the occlusion (stroke: without occlusion, 11.68 ± 5.83%MVC vs. with occlusion, 11.11 ± 5.26%MVC; control: 11.87 ± 5.63 vs. 11.28 ± 5.29%MVC). Resting twitch amplitudes declined similarly for both groups in response to whole leg occlusion (stroke: 29.16 ± 6.88 vs. 25.75 ± 6.78 Nm; control: 38.80 ± 13.23 vs 30.14 ± 9.64 Nm). Controls had a greater exponential decline (lower time constant) in oxygen saturation compared with the stroke group (stroke time constant, 22.90 ± 10.26 min vs. control time constant, 5.46 ± 4.09 min; P < 0.001). Ischemia of the muscle resulted in greater neural inhibition of paretic motor units compared with controls and may contribute to deficient muscle activation poststroke. NEW & NOTEWORTHY Hyperexcitable inhibitory sensory pathways sensitive to ischemia may play a role in deficient motor unit activation post stroke. Using high-density surface electromyography recordings to detect motor unit firing instances, we show that ischemia of the exercising muscle results in greater inhibition of paretic motor unit firing rates compared with controls. These findings are impactful to neurophysiologists and clinicians because they implicate a novel mechanism of force-generating impairment poststroke that likely exacerbates baseline weakness.


2021 ◽  
Author(s):  
Leon A Steiner ◽  
Andrea A Kuehn ◽  
Joerg RP Geiger ◽  
Henrik Alle ◽  
Milos Popovic ◽  
...  

Background: Deep brain stimulation (DBS) provides symptomatic relief in a growing number of neurological indications, but local synaptic dynamics in response to electrical stimulation that may relate to its mechanism of action have not been fully characterized. Objective: The objectives of this study were to (1) study local synaptic dynamics during high frequency extracellular stimulation of the subthalamic nucleus (STN), and (2) compare STN synaptic dynamics with those of the neighboring substantia nigra pars reticulata (SNr). Methods: Two microelectrodes were advanced into the STN and SNr of patients undergoing DBS surgery for PD. Neuronal firing and evoked field potentials (fEPs) were recorded with one microelectrode during stimulation from an adjacent microelectrode. Results: Excitatory and inhibitory fEPs could be discerned within the STN and their amplitudes predicted bidirectional effects on neuronal firing (p = .007). There were no differences between STN and SNr inhibitory fEP dynamics at low stimulation frequencies (p > .999). However, inhibitory neuronal responses were sustained over time in STN during high frequency stimulation, but not SNr (p < .001) where depression of inhibitory input was coupled with a return of neuronal firing (p = .003). Interpretation: Persistent inhibitory input to the STN suggests a local synaptic mechanism for the suppression of subthalamic firing during high frequency stimulation. Moreover, differences in the resiliency versus vulnerability of inhibitory inputs to the STN and SNr suggest a projection source- and frequency-specificity for this mechanism. The feasibility of targeting electrophysiologically-identified neural structures may provide insight into how DBS achieves frequency-specific modulation of neuronal projections.


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