scholarly journals Inhibitory Effect of Apomorphine on Focal and Nonfocal Plasticity in the Human Motor Cortex

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 718
Author(s):  
Shane M. Fresnoza ◽  
Giorgi Batsikadze ◽  
Lynn Elena Müller ◽  
Constanze Rost ◽  
Michael Chamoun ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Motor Evoked Potentials ◽  
Specific Effect ◽  
Long Term Potentiation ◽  
Receptor Activation ◽  
Inhibitory Effect ◽  
Receptor Subtype ◽  
Human Motor Cortex ◽  
Motor Cortex Plasticity

Dopamine is crucial for neuroplasticity, which is considered to be the neurophysiological foundation of learning and memory. The specific effect of dopamine on plasticity such as long-term potentiation (LTP) and long-term depression (LTD) is determined by receptor subtype specificity, concentration level, and the kind of plasticity induction technique. In healthy human subjects, the dopamine precursor levodopa (L-DOPA) exerts a dosage-dependent non-linear effect on motor cortex plasticity. Low and high dosage L-DOPA impaired or abolished plasticity, while medium-dose preserved and reversed plasticity in previous studies. Similar dosage-dependent effects were also observed for selective D1-like and D2-like receptor activation that favor excitatory and inhibitory plasticity, respectively. However, such a dosage-dependent effect has not been explored for a nonselective dopamine agonist such as apomorphine in humans. To this aim, nonfocal and focal motor cortex plasticity induction using paired associative stimulation (PAS) and transcranial direct current stimulation (tDCS) were performed respectively in healthy participants under 0.1, 0.2, 0.3 mg apomorphine or placebo drug. Transcranial magnetic stimulation-elicited motor-evoked potentials were used to monitor motor cortical excitability alterations. We hypothesized that, similar to L-DOPA, apomorphine will affect motor cortex plasticity. The results showed that apomorphine with the applied dosages has an inhibitory effect for focal and nonfocal LTP-like and LTD-like plasticity, which was either abolished, diminished or reversed. The detrimental effect on plasticity induction under all dosages of apomorphine suggests a predominantly presynaptic mechanism of action of these dosages.

146. Preceding repetitive stimulation diminishes long-term potentiation-like plasticity in human motor cortex

2009 ◽  
Vol 120 (1) ◽  
pp. e61
Author(s):  
I. Delvendahl ◽  
N. Jung ◽  
M. Cronjaeger ◽  
F. Mainberger ◽  
N. Kuhnke ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Long Term Potentiation ◽  
Repetitive Stimulation ◽  
Human Motor Cortex ◽  
Term Potentiation ◽  
Human Motor

Inducing Homeostatic-Like Plasticity in Human Motor Cortex Through Converging Corticocortical Inputs

2009 ◽  
Vol 102 (6) ◽  
pp. 3180-3190 ◽  
Author(s):  
Monika Pötter-Nerger ◽  
Sarah Fischer ◽  
Claudia Mastroeni ◽  
Sergiu Groppa ◽  
Günther Deuschl ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Median Nerve ◽  
Primary Motor Cortex ◽  
Premotor Cortex ◽  
Long Term Potentiation ◽  
Corticospinal Excitability ◽  
Human Motor Cortex ◽  
Induced Changes ◽  
Homeostatic Response

Transcranial stimulation techniques have revealed homeostatic-like metaplasticity in the hand area of the human primary motor cortex (M1HAND) that controls stimulation-induced changes in corticospinal excitability. Here we combined two interventional protocols that induce long-term depression (LTD)–like or long-term potentiation (LTP)–like plasticity in left M1HAND through different afferents. We hypothesized that the left M1HAND would integrate LTP- and LTD-like plasticity in a homeostatic fashion. In ten healthy volunteers, low-intensity repetitive transcranial magnetic stimulation (rTMS) of the left dorsal premotor cortex (PMD) was first applied to produce an LTP-like increase (5 Hz rTMS) or LTD-like decrease (1 Hz rTMS) in corticospinal excitability in left M1HAND via premotor-to-motor inputs. Following PMD rTMS, paired-associative stimulation (PAS) was applied to the right median nerve and left M1HAND to induce spike-time–dependent plasticity in sensory-to-motor inputs to left M1HAND. We adjusted the interstimulus interval to the N20 latency of the median nerve somatosensory-evoked cortical potential to produce an LTP-like increase (PASN20+2ms) or an LTD-like decrease (PASN20−5ms) in corticospinal excitability. The amplitude of motor-evoked potentials was recorded from intrinsic hand muscles to assess stimulation-induced changes in corticospinal excitability. Premotor-to-motor preconditioning triggered a homeostatic response to subsequent sensory-to-motor PAS. After facilitatory 5 Hz rTMS, “facilitatory” PASN20+2ms suppressed corticospinal excitability. Likewise, “inhibitory” PASN20−5ms facilitated corticospinal excitability after “inhibitory” 1 Hz rTMS. There was a negative linear relationship between the excitability changes induced by PMD rTMS and those elicited by subsequent PAS. Excitability changes were not paralleled by changes in performance during a finger-tapping task. These results provide evidence for a homeostatic response pattern in the human M1HAND that integrates acute plastic changes evoked through different “input channels.”

Conditions for the induction of long-term potentiation in layer II/III horizontal connections of the rat motor cortex

1996 ◽  
Vol 75 (5) ◽  
pp. 1765-1778 ◽  
Author(s):  
G. Hess ◽  
C. D. Aizenman ◽  
J. P. Donoghue
Keyword(s):  
Motor Cortex ◽  
Field Potential ◽  
Long Term Potentiation ◽  
Receptor Activation ◽  
Intracellular Recordings ◽  
Recording Site ◽  
Horizontal Connections ◽  
Term Potentiation ◽  
Activity Dependent

1. The present studies investigated conditions for the induction of long-term potentiation (LTP) in the local horizontal pathways of layers II/III in the primary motor cortex (MI) of the adult rat. Field potential and intracellular recordings demonstrated synaptic interactions across the superficial layers within MI that could be enhanced transiently by focal application of the gamma-aminobuturic acid-A receptor antagonist bicuculline methiodide (Bic) at the recording site. 2. Field potentials evoked in the superficial MI horizontal pathways increased in amplitude after tetanizing, theta burst stimulation (TBS), but only when Bic was applied transiently at the recording site immediately before TBS. In the absence of Bic, TBS failed to produce long-lasting increases in horizontally evoked field responses. By contrast, TBS delivery during focal Bic application increased field potential amplitudes by 25-35% when measured 25-30 min after stimulation. The amount of potentiation was greater when two converging horizontal inputs were stimulated together but was not increased with higher intensity stimulation. Persistent effects of Bic application alone were evident. However, these effects were small unless Bic application continued until evoked field potential amplitude increase exceeded 200% of baseline. 3. The synaptic nature of field potential increases were confirmed using intracellular recordings of layer II/III neurons located near field potential electrodes. 4. LTP also could be induced without Bic application by cotetanization of vertical pathways simultaneously with horizontal activation. Vertical conditioning alone at 2 Hz, which affects inhibitory efficacy, was shown to transiently relieve depression of successive responses that ordinarily occurs during a burst of three horizontal stimuli. These results suggest that LTP of horizontal pathways may be regulated by spatiotemporal interactions between horizontal and vertical pathways. 5. Horizontal LTP was blocked reversibly by bath application of the N-methyl-D-aspartate (NMDA) antagonist 2-amino-5-phosphonovaleric acid, thereby implicating NMDA-receptor activation in LTP induction for these pathways. 6. The results confirm and extend our previous finding that the potential for activity-dependent modification of synaptic connections exists within the intrinsic horizontal connections of the superficial cortical layers. Synaptic modification across horizontally connected neurons appears to be regulated both by the arrangement of intrinsic circuitry and by the availability of mechanisms for modification at individual synapses. The properties of horizontal connections indicate that they form a spatial substrate and provide an activity-dependent mechanism for plasticity of adult cortical representations.

Exploring the effect of inducing long-term potentiation in the human motor cortex on motor learning

2011 ◽  
Vol 4 (3) ◽  
pp. 137-144 ◽  
Author(s):  
Tarek K. Rajji ◽  
Shi-Kai Liu ◽  
Marina V. Frantseva ◽  
Benoit H. Mulsant ◽  
Jessica Thoma ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Motor Learning ◽  
Long Term Potentiation ◽  
Human Motor Cortex ◽  
Term Potentiation ◽  
Human Motor

Mechanisms of human motor cortex facilitation induced by subthreshold 5-Hz repetitive transcranial magnetic stimulation

2013 ◽  
Vol 109 (12) ◽  
pp. 3060-3066 ◽  
Author(s):  
Martin Sommer ◽  
Milena Rummel ◽  
Christoph Norden ◽  
Holger Rothkegel ◽  
Nicolas Lang ◽  
...  
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Motor Cortex ◽  
Magnetic Stimulation ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Long Term Potentiation ◽  
Human Motor Cortex ◽  
Term Potentiation ◽  
Human Motor ◽  
Extensor Carpi Radialis

Our knowledge about the mechanisms of human motor cortex facilitation induced by repetitive transcranial magnetic stimulation (rTMS) is still incomplete. Here we used pharmacological conditioning with carbamazepine, dextrometorphan, lorazepam, and placebo to elucidate the type of plasticity underlying this facilitation, and to probe if mechanisms reminiscent of long-term potentiation are involved. Over the primary motor cortex of 10 healthy subjects, we applied biphasic rTMS pulses of effective posterior current direction in the brain. We used six blocks of 200 pulses at 5-Hz frequency and 90% active motor threshold intensity and controlled for corticospinal excitability changes using motor-evoked potential (MEP) amplitudes and latencies elicited by suprathreshold pulses before, in between, and after rTMS. Target muscle was the dominant abductor digiti minimi muscle; we coregistered the dominant extensor carpi radialis muscle. We found a lasting facilitation induced by this type of rTMS. The GABAergic medication lorazepam and to a lesser extent the ion channel blocker carbamazepine reduced the MEP facilitation after biphasic effective posteriorly oriented rTMS, whereas the N-methyl-d-aspartate receptor-antagonist dextrometorphan had no effect. Our main conclusion is that the mechanism of the facilitation induced by biphasic effective posterior rTMS is more likely posttetanic potentiation than long-term potentiation. Additional findings were prolonged MEP latency under carbamazepine, consistent with sodium channel blockade, and larger MEP amplitudes from extensor carpi radialis under lorazepam, suggesting GABAergic involvement in the center-surround balance of excitability.

scholarly journals Blockade of Motor Cortical Long-Term Potentiation Induction by Glutamatergic Dysfunction Causes Abnormal Neurobehavior in an Experimental Subarachnoid Hemorrhage Model

2021 ◽  
Vol 15 ◽  
Author(s):  
Minoru Fujiki ◽  
Kazuhiro Kuga ◽  
Harushige Ozaki ◽  
Yukari Kawasaki ◽  
Hirotaka Fudaba
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Motor Evoked Potentials ◽  
Long Term Potentiation ◽  
Receptor Activation ◽  
Functional Evaluation ◽  
Evaluation Tool ◽  
Mk 801 ◽  
Term Potentiation ◽  
Motor Cortical

Subarachnoid hemorrhage (SAH) is a life-threatening condition that can also lead to permanent paralysis. However, the mechanisms that underlying neurobehavioral deficits after SAH have not been fully elucidated. As theta burst stimulation (TBS) can induce long-term potentiation (LTP) in the motor cortex, we tested its potential as a functional evaluation tool after experimentally induced SAH. Motor cortical inter-neuronal excitability was evaluated in anesthetized rats after 200 Hz-quadripulse TBS (QTS5), 200 Hz-quadripulse stimulation (QPS5), and 400 Hz-octapulse stimulation (OPS2.5). Furthermore, correlation between motor cortical LTP and N-methyl-D-aspartate-receptor activation was evaluated using MK-801, a NMDA-receptor antagonist. We evaluated inhibition-facilitation configurations [interstimulus interval: 3 ms; short-latency intracortical inhibition (SICI) and 11 ms; intracortical facilitation (ICF)] with paired electrical stimulation protocols and the effect of TBS paradigm on continuous recording of motor-evoked potentials (MEPs) for quantitative parameters. SAH and MK-801 completely blocked ICF, while SICI was preserved. QTS5, QPS5, and OPS2.5 facilitated continuous MEPs, persisting for 180 min. Both SAH and MK-801 completely blocked MEP facilitations after QPS5 and OPS2.5, while MEP facilitations after QTS5 were preserved. Significant correlations were found among neurological scores and 3 ms-SICI rates, 11 ms-ICF rates, and MEP facilitation rates after 200 Hz-QTS5, 7 days after SAH (R2 = 0.6236; r = −0.79, R2 = 0.6053; r = −0.77 and R2 = 0.9071; r = 0.95, p < 0.05, respectively). Although these findings need to be verified in humans, our study demonstrates that the neurophysiological parameters 3 ms-SICI, 11 ms-ICF, and 200 Hz-QTS5-MEPs may be useful surrogate quantitative biomarkers for assessing inter-neuronal function after SAH.

scholarly journals Inducing LTD-Like Effect in the Human Motor Cortex with Low Frequency and Very Short Duration Paired Associative Stimulation: An Exploratory Study

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Prachaya Srivanitchapoom ◽  
Jung E. Park ◽  
Nivethida Thirugnanasambandam ◽  
Pattamon Panyakaew ◽  
Vesper Fe Marie Ramos ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Motor Cortex ◽  
Short Duration ◽  
Repeated Measures ◽  
Low Frequency ◽  
Long Term Potentiation ◽  
Paired Associative Stimulation ◽  
Human Motor Cortex ◽  
Human Motor

Introduction.Paired associative stimulation (PAS) is an established technique to investigate synaptic plasticity in the human motor cortex (M1). Classically, to induce long-term depression- (LTD-) or long-term potentiation-like effects in the human M1, studies have used low frequency and long duration trains of PAS. In the present study, we explored an LTD-like effect using very short duration and low frequency ofPAS10 msprotocols in human M1.Methods.Six protocols of low frequencyPAS10 ms(ranging from 0.2 Hz to 1 Hz) were investigated with very short durations of 1 and 2 minutes stimulation. Six healthy volunteers were included in each protocol. We obtained motor-evoked potentials from right abductor pollicis brevis muscle before and after applyingPAS10 msup to 30 minutes. After we foundPAS10 msprotocol which induced an LTD-like effect, we tested that protocol on additional 5 subjects.Results.One-way repeated-measures ANOVA showed that only the group of 1-minute stimulation of 0.25 Hz induced an LTD-like effect. When adding the additional subjects, the effect remained and lasted for 30 minutes.Conclusion.Low frequency and very short duration ofPAS10 mspotentially induced an LTD-like effect in human M1. With further verification, this method might be useful for research relating to synaptic plasticity by reducing the duration of study and minimizing subject discomfort.

A Temporally Asymmetric Hebbian Rule Governing Plasticity in the Human Motor Cortex

2003 ◽  
Vol 89 (5) ◽  
pp. 2339-2345 ◽  
Author(s):  
Alexander Wolters ◽  
Friedhelm Sandbrink ◽  
Antje Schlottmann ◽  
Erwin Kunesch ◽  
Katja Stefan ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Median Nerve ◽  
Cortical Excitability ◽  
Long Term Potentiation ◽  
Long Term Depression ◽  
Human Motor Cortex ◽  
Motor Cortical Excitability ◽  
Human Motor ◽  
Motor Cortical

Synaptic plasticity is conspicuously dependent on the temporal order of the pre- and postsynaptic activity. Human motor cortical excitability can be increased by a paired associative stimulation (PAS) protocol. Here we show that it can also be decreased by minimally changing the interval between the two associative stimuli. Corticomotor excitability of the abductor pollicis brevis (APB) representation was tested before and after repetitively pairing of single right median nerve simulation with single pulse transcranial magnetic stimulation (TMS) delivered over the optimal site for activation of the contralateral APB. Following PAS, depression of TMS-evoked motor-evoked potentials (MEPs) was induced only when the median nerve stimulation preceded the TMS pulse by 10 ms, while enhancement of cortical excitability was induced using an interstimulus interval of 25 ms, suggesting an important role of the sequence of cortical events triggered by the two stimulation modalities. Experiments using F-wave studies and electrical brain stem stimulation indicated that the site of the plastic changes underlying the decrease of MEP amplitudes following PAS (10 ms) was within the motor cortex. MEP amplitudes remained depressed for approximately 90 min. The decrease of MEP amplitudes was blocked when PAS(10 ms) was performed under the influence of dextromethorphan, an N-methyl-d-aspartate-receptor antagonist, or nimodipine, an L-type voltage-gated calcium-channel antagonist. The physiological profile of the depression of human motor cortical excitability following PAS(10 ms) suggests long-term depression of synaptic efficacy to be involved. Together with earlier findings, this study suggests that strict temporal Hebbian rules govern the induction of long-term potentiation/long-term depression-like phenomena in vivo in the human primary motor cortex.

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