Cellular Mechanisms Preventing Sustained Activation of Cortex During Subcortical High-Frequency Stimulation

2006 ◽  
Vol 96 (2) ◽  
pp. 613-621 ◽  
Author(s):  
Karl J. Iremonger ◽  
Trent R. Anderson ◽  
Bin Hu ◽  
Zelma H. T. Kiss
Keyword(s):  
Motor Cortex ◽  
High Frequency ◽  
Cortical Neurons ◽  
Primary Motor Cortex ◽  
Brain Slices ◽  
Subcortical White Matter ◽  
High Frequency Stimulation ◽  
Cellular Mechanisms ◽  
Ventral Thalamus ◽  
Frequency Stimulation

Axonal excitation has been proposed as a key mechanism in therapeutic brain stimulation. In this study we examined how high-frequency stimulation (HFS) of subcortical white matter tracts projecting to motor cortex affects downstream postsynaptic responses in cortical neurons. Whole cell recordings were performed in the primary motor cortex (M1) and ventral thalamus of rat brain slices. In M1, neurons showed only an initial depolarization in response to HFS, after which the membrane potential returned to prestimulation levels. The prolonged suppression of excitation during stimulation was neither associated with GABAergic inhibition nor complete action potential failure in stimulated axons. Instead we found that HFS caused a depression of excitatory synaptic currents in postsynaptic neurons that was specific to the stimulated subcortical input. These data are consistent with the hypothesis that axonal HFS produces a functional deafferentation of postsynaptic targets likely from depletion of neurotransmitter.

Cellular Mechanisms Underlying Antiepileptic Effects of Low- and High-Frequency Electrical Stimulation in Acute Epilepsy in Neocortical Brain Slices In Vitro

2007 ◽  
Vol 97 (3) ◽  
pp. 1887-1902 ◽  
Author(s):  
Yitzhak Schiller ◽  
Yael Bankirer
Keyword(s):  
Electrical Stimulation ◽  
High Frequency ◽  
Brain Slices ◽  
Low Frequency ◽  
High Frequency Stimulation ◽  
Dependent Manner ◽  
Cellular Mechanisms ◽  
Epileptiform Discharges ◽  
Frequency Stimulation

Approximately 30% of epilepsy patients suffer from drug-resistant epilepsy. Direct electrical stimulation of the epileptogenic zone is a potential new treatment modality for this devastating disease. In this study, we investigated the effect of two electrical stimulation paradigms, sustained low-frequency stimulation and short trains of high-frequency stimulation, on epileptiform discharges in neocortical brain slices treated with either bicuculline or magnesium-free extracellular solution. Sustained low-frequency stimulation (5–30 min of 0.1- to 5-Hz stimulation) prevented both interictal-like discharges and seizure-like events in an intensity-, frequency-, and distance-dependent manner. Short trains of high-frequency stimulation (1–5 s of 25- to 200-Hz stimulation) prematurely terminated seizure-like events in a frequency-, intensity-, and duration-dependent manner. Roughly one half the seizures terminated within the 100-Hz stimulation train ( P < 0.01 compared with control), whereas the remaining seizures were significantly shortened by 53 ± 21% ( P < 0.01). Regarding the cellular mechanisms underlying the antiepileptic effects of electrical stimulation, both low- and high-frequency stimulation markedly depressed excitatory postsynaptic potentials (EPSPs). The EPSP amplitude decreased by 75 ± 3% after 10-min, 1-Hz stimulation and by 86 ± 6% after 1-s, 100-Hz stimulation. Moreover, partial pharmacological blockade of ionotropic glutamate receptors was sufficient to suppress epileptiform discharges and enhance the antiepileptic effects of stimulation. In conclusion, this study showed that both low- and high-frequency electrical stimulation possessed antiepileptic effects in the neocortex in vitro, established the parameters determining the antiepileptic efficacy of both stimulation paradigms, and suggested that the antiepileptic effects of stimulation were mediated mostly by short-term synaptic depression of excitatory neurotransmission.

scholarly journals Fidelity of frequency and phase entrainment of circuit-level spike activity during DBS

2015 ◽  
Vol 114 (2) ◽  
pp. 825-834 ◽  
Author(s):  
Filippo Agnesi ◽  
Abirami Muralidharan ◽  
Kenneth B. Baker ◽  
Jerrold L. Vitek ◽  
Matthew D. Johnson
Keyword(s):  
Motor Cortex ◽  
Spike Activity ◽  
High Frequency ◽  
Rhesus Macaques ◽  
High Frequency Stimulation ◽  
Stimulus Pulse ◽  
Low Pass ◽  
Frequency Stimulation ◽  
Stn Dbs ◽  
Over Time

High-frequency stimulation is known to entrain spike activity downstream and upstream of several clinical deep brain stimulation (DBS) targets, including the cerebellar-receiving area of thalamus (VPLo), subthalamic nucleus (STN), and globus pallidus (GP). Less understood are the fidelity of entrainment to each stimulus pulse, whether entrainment patterns are stationary over time, and how responses differ among DBS targets. In this study, three rhesus macaques were implanted with a single DBS lead in VPLo, STN, or GP. Single-unit spike activity was recorded in the resting state in motor cortex during VPLo DBS, in GP during STN DBS, and in STN and pallidal-receiving area of motor thalamus (VLo) during GP DBS. VPLo DBS induced time-locked spike activity in 25% ( n = 15/61) of motor cortex cells, with entrained cells following 7.5 ± 7.4% of delivered pulses. STN DBS entrained spike activity in 26% ( n = 8/27) of GP cells, which yielded time-locked spike activity for 8.7 ± 8.4% of stimulus pulses. GP DBS entrained 67% ( n = 14/21) of STN cells and 32% ( n = 19/59) of VLo cells, which showed a higher fraction of pulses effectively inhibiting spike activity (82.0 ± 9.6% and 86.1 ± 16.6%, respectively). Latency of phase-locked spike activity increased over time in motor cortex (58%, VPLo DBS) and to a lesser extent in GP (25%, STN DBS). In contrast, the initial inhibitory phase observed in VLo and STN during GP DBS remained stable following stimulation onset. Together, these data suggest that circuit-level entrainment is low-pass filtered during high-frequency stimulation, most notably for glutamatergic pathways. Moreover, phase entrainment is not stationary or consistent at the circuit level for all DBS targets.

scholarly journals Differences in Nicotine Encoding Dopamine Release between the Striatum and Shell Portion of the Nucleus Accumbens

2018 ◽  
Vol 28 (3) ◽  
pp. 248-261 ◽  
Author(s):  
Yuan-Hao Chen ◽  
Bon-Jour Lin ◽  
Tsung-Hsun Hsieh ◽  
Tung-Tai Kuo ◽  
Jonathan Miller ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
High Frequency ◽  
Dopamine Release ◽  
Brain Slices ◽  
Dorsal Striatum ◽  
High Frequency Stimulation ◽  
Sprague Dawley ◽  
Frequency Stimulation ◽  
Da Release

The aim of this work was to determine the effect of nicotine desensitization on dopamine (DA) release in the dorsal striatum and shell of the nucleus accumbens (NAc) from brain slices. In vitro fast-scan cyclic voltammetry analysis was used to evaluate dopamine release in the dorsal striatum and the NAc shell of Sprague–Dawley rats after infusion of nicotine, a nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine (Mec), and an α4β2 cholinergic receptor antagonist (DHβe). DA release related to nicotine desensitization in the striatum and NAc shell was compared. In both structures, tonic release was suppressed by inhibition of the nicotine receptor (via Mec) and the α4β2 receptor (via DHβe). Paired-pulse ratio (PPR) was facilitated in both structures after nicotine and Mec infusion, and this facilitation was suppressed by increasing the stimulation interval. After variable frequency stimulation (simulating phasic burst), nicotine infusion induced significant augmentation of DA release in the striatum that was not seen in the absence of nicotine. In contrast, nicotine reduced phasic DA release in NAc, although frequency augmentation was seen both with and without nicotine. Evaluation of DA release evoked by various trains (high-frequency stimulation (HFS) 100 Hz) of high-frequency stimulation revealed significant enhancement after a train of three or more pulses in the striatum and NAc. The concentration differences between tonic and phasic release related to nicotine desensitization were more pronounced in the NAc shell. Nicotine desensitization is associated with suppression of tonic release of DA in both the striatum and NAc shell that may occur via the α4β2 subtype of nAChR, whereas phasic frequency-dependent augmentation and HFS-related gating release is more pronounced in the striatum than in the NAc shell. Differences between phasic and tonic release associated with nicotine desensitization may underlie processing of reward signals in the NAc shell, and this may have major implications for addictive behavior.

scholarly journals Xenon Attenuates Hippocampal Long-term Potentiation by Diminishing Synaptic and Extrasynaptic N -methyl-D-aspartate Receptor Currents

2012 ◽  
Vol 116 (3) ◽  
pp. 673-682 ◽  
Author(s):  
Stephan Kratzer ◽  
Corinna Mattusch ◽  
Eberhard Kochs ◽  
Matthias Eder ◽  
Rainer Haseneder ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
High Frequency ◽  
Brain Slices ◽  
Long Term Potentiation ◽  
High Frequency Stimulation ◽  
Field Potentials ◽  
Aspartate Receptor ◽  
Term Potentiation ◽  
Frequency Stimulation

Background The memory-blocking properties of general anesthetics are of high clinical relevance and scientific interest. The inhalational anesthetic xenon antagonizes N-methyl-D-aspartate (NMDA) receptors. It is unknown if xenon affects long-term potentiation (LTP), a cellular correlate for memory formation. In hippocampal brain slices, the authors investigated in area CA1 whether xenon affects LTP, NMDA receptor-mediated neurotransmission, and intracellular calcium concentrations. Methods In sagittal murine hippocampal brain slices, the authors investigated the effects of xenon on LTP by recording excitatory postsynaptic field potentials. Using fluorometric calcium imaging, the authors tested the influence of xenon on calcium influx during high-frequency stimulation. In addition, using the patch-clamp technique, the xenon effect on synaptic and extrasynaptic NMDA receptors and L-type calcium channels was examined. Results In the absence of xenon, high-frequency stimulation reliably induced LTP and potentiated field potential slopes to (mean ± SEM) 127.2 ± 5.8% (P &lt; 0.001). In the presence of xenon, high-frequency stimulation induced only a short-term potentiation, and field potentials returned to baseline level after 15-20 min (105.9 ± 2.9%; P = 0.090). NMDA receptor-mediated excitatory postsynaptic currents were reduced reversibly by xenon to 65.9 ± 9.4% (P = 0.007) of control. When extrasynaptic receptors were activated, xenon decreased NMDA currents to 58.2 ± 5.8% (P &lt; 0.001). Xenon reduced the increase in intracellular calcium during high-frequency stimulation without affecting L-type calcium channels. Conclusions N-methyl-D-aspartate receptor activation is crucial for the induction of CA1 LTP. Thus, the depression of NMDA receptor-mediated neurotransmission presumably contributes to the blockade of LTP under xenon. Because LTP is assumed to be involved in learning and memory, its blockade might be a key mechanism for xenon's amnestic properties.

Cellular mechanisms of fatigue in skeletal muscle

1991 ◽  
Vol 261 (2) ◽  
pp. C195-C209 ◽  
Author(s):  
H. Westerblad ◽  
J. A. Lee ◽  
J. Lannergren ◽  
D. G. Allen
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
High Frequency ◽  
Force Production ◽  
High Frequency Stimulation ◽  
Tetanic Stimulation ◽  
Cellular Mechanisms ◽  
Frequency Stimulation ◽  
T Tubules ◽  
Underlying Mechanisms

Prolonged activation of skeletal muscle leads to a decline of force production known as fatigue. In this review we outline the ionic and metabolic changes that occur in muscle during prolonged activity and focus on how these changes might lead to reduced force. We discuss two distinct types of fatigue: fatigue due to continuous high-frequency stimulation and fatigue due to repeated tetanic stimulation. The causes of force decline are considered under three categories: 1) reduced Ca2+ release from the sarcoplasmic reticulum, 2) reduced myofibrillar Ca2+ sensitivity, and 3) reduced maximum Ca(2+)-activated tension. Reduced Ca2+ release can be due to impaired action potential propagation in the T tubules, and this is a principal cause of the tension decline with continuous tetanic stimulation. Another type of failing Ca2+ release, which is homogeneous across the fibers, is prominent with repeated tetanic stimulation; the underlying mechanisms of this reduction are not fully understood, although several possibilities emerge. Changes in intracellular metabolites, particularly increased concentration of Pi and reduced pH, lead to reduced Ca2+ sensitivity and reduced maximum tension, which make an important contribution to the force decline, especially with repeated tetanic stimulation.

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