Inhibitory Mechanisms in the Motor Cortical Circuit

2017 ◽  
pp. 67-74
Author(s):  
Hugo Merchant ◽  
Apostolos P. Georgopoulos
Keyword(s):  
Motor Control ◽  
Primary Motor Cortex ◽  
Pyramidal Cells ◽  
Local Inhibition ◽  
Inhibitory Mechanisms ◽  
Gating Mechanism ◽  
Cortical Circuit ◽  
Motor Cortical ◽  
Behaving Monkeys

Inhibitory mechanisms are crucial for the integrated operation of the motor cortical circuit. Local inhibition is exerted by interneurons that are GABAergic, nonpyramidal cells with short, nonprojecting axons. Interneurons can be classified into at least two groups: fast-spiking (FS) neurons and instrinsic bursting (IB) neurons. In the primary motor cortex, FS cells may sculpe the tuning dispersion of directionally selective putative pyramidal cells during reaching in behaving monkeys. Analysis of putative interneuronal activity also allowed to discard the role of inhibition as a gating mechanism in motor control. The development of high-density, semichronic electrode systems for extracellular recordings in behaving primates will allow a closer investigation of the role of interneuronal inhibition in directional tuning and voluntary motor control. The results discussed in this chapter agree with the authors’ proposal that local inhibitory mechanisms may be intimately involved in controlling the directional accuracy and speed of the reaching movement.

The Pathophysiology of Tics; An Evolving Story

2020 ◽  
Vol 15 (2) ◽  
pp. 92-123 ◽  
Author(s):  
Harvey S. Singer ◽  
Farhan Augustine
Keyword(s):  
Motor Control ◽  
Primary Motor Cortex ◽  
Scientific Data ◽  
Anatomical Site ◽  
Pathophysiological Mechanism ◽  
Model Studies ◽  
Complex Disorder ◽  
Complex Integration ◽  
Motor Movements

Background: Tics, defined as quick, rapid, sudden, recurrent, non-rhythmic motor movements or vocalizations are required components of Tourette Syndrome (TS) - a complex disorder characterized by the presence of fluctuating, chronic motor and vocal tics, and the presence of co-existing neuropsychological problems. Despite many advances, the underlying pathophysiology of tics/TS remains unknown. Objective: To address a variety of controversies surrounding the pathophysiology of TS. More specifically: 1) the configuration of circuits likely involved; 2) the role of inhibitory influences on motor control; 3) the classification of tics as either goal-directed or habitual behaviors; 4) the potential anatomical site of origin, e.g. cortex, striatum, thalamus, cerebellum, or other(s); and 5) the role of specific neurotransmitters (dopamine, glutamate, GABA, and others) as possible mechanisms (Abstract figure). Methods: Existing evidence from current clinical, basic science, and animal model studies are reviewed to provide: 1) an expanded understanding of individual components and the complex integration of the Cortico-Basal Ganglia-Thalamo-Cortical (CBGTC) circuit - the pathway involved with motor control; and 2) scientific data directly addressing each of the aforementioned controversies regarding pathways, inhibition, classification, anatomy, and neurotransmitters. Conclusion: Until a definitive pathophysiological mechanism is identified, one functional approach is to consider that a disruption anywhere within CBGTC circuitry, or a brain region inputting to the motor circuit, can lead to an aberrant message arriving at the primary motor cortex and enabling a tic. Pharmacologic modulation may be therapeutically beneficial, even though it might not be directed toward the primary abnormality.

scholarly journals Synaptically Recruited Apical Currents Are Required to Initiate Axonal and Apical Spikes in Hippocampal Pyramidal Cells: Modulation by Inhibition

2005 ◽  
Vol 93 (2) ◽  
pp. 909-918 ◽  
Author(s):  
S. Canals ◽  
L. López-Aguado ◽  
O. Herreras
Keyword(s):  
Action Potentials ◽  
Pyramidal Cells ◽  
Excitatory Input ◽  
Synaptic Potentials ◽  
Local Inhibition ◽  
Voltage Dependent ◽  
Cell Firing

Dendritic voltage-dependent currents and inhibition modulate the information flow between synaptic and decision areas. Subthreshold and spike currents are sequentially recruited by synaptic potentials in the apical shaft of pyramidal cells, which may also decide cell output. We studied the global role of proximal apical recruited currents on cell output in vitro and in the anesthetized rat after local blockade of Na+ currents in the axon initial segment (AIS) or the proximal apical shaft and their modulation by inhibition. Microejection of TTX, field potentials, and intrasomatic and intradendritic recordings were employed. Dendritic population spikes (PSs) were much smaller in vitro, but the gross relations between synaptic and active currents are similar to in vivo. Activation of Schaffer collaterals triggered PSs and action potentials (APs) in the apical shaft that fully propagated to the axon. However, the specific blockade of proximal Na+ currents avoided cell firing, although antidromic PSs and APs readily invaded somata. The somatic depolarization of subthreshold excitatory postsynaptic potentials (EPSPs) also decreased to about 50%. These results were not due to decreased excitatory input by TTX. However, when GABAA inhibition was locally removed, Schaffer synaptic currents skipped the proximal dendrite and fired somatic PSs, although initiated at the AIS. It is concluded that apical currents recruited en passant by Schaffer synaptic potentials in the apical shaft constitute a necessary amplifier for this input to cause output decision. Local inhibition decides when and where an AP will initiate, constituting an efficient mechanism to discriminate and weight different inputs.

scholarly journals Competition, Conflict and Change of Mind: A Role of GABAergic Inhibition in the Primary Motor Cortex

2022 ◽  
Vol 15 ◽  
Author(s):  
Bastien Ribot ◽  
Aymar de Rugy ◽  
Nicolas Langbour ◽  
Anne Duron ◽  
Michel Goillandeau ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Primary Motor Cortex ◽  
Silent Period ◽  
Single Pulse ◽  
Electromyographic Activity ◽  
Continuous Control ◽  
Gabaergic Inhibition ◽  
Inhibitory Mechanisms ◽  
Post Onset

Deciding between different voluntary movements implies a continuous control of the competition between potential actions. Many theories postulate a leading role of prefrontal cortices in this executive function, but strong evidence exists that a motor region like the primary motor cortex (M1) is also involved, possibly via inhibitory mechanisms. This was already shown during the pre-movement decision period, but not after movement onset. For this pilot experiment we designed a new task compatible with the dynamics of post-onset control to study the silent period (SP) duration, a pause in electromyographic activity after single-pulse transcranial magnetic stimulation that reflects inhibitory mechanisms. A careful analysis of the SP during the ongoing movement indicates a gradual increase in inhibitory mechanisms with the level of competition, consistent with an increase in mutual inhibition between alternative movement options. However, we also observed a decreased SP duration for high-competition trials associated with change-of-mind inflections in their trajectories. Our results suggest a new post-onset adaptive process that consists in a transient reduction of GABAergic inhibition within M1 for highly conflicting situations. We propose that this reduced inhibition softens the competition between concurrent motor options, thereby favoring response vacillation, an adaptive strategy that proved successful at improving behavioral performance.

scholarly journals Structure of the full-length human Pannexin1 channel and insights into its role in pyroptosis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Sensen Zhang ◽  
Baolei Yuan ◽  
Jordy Homing Lam ◽  
Jun Zhou ◽  
Xuan Zhou ◽  
...  
Keyword(s):  
Md Simulation ◽  
Potential Role ◽  
Md Simulations ◽  
Full Length ◽  
Inflammasome Activation ◽  
Simulation Studies ◽  
Cryo Electron Microscopy ◽  
Gating Mechanism ◽  
Atp Efflux

AbstractPannexin1 (PANX1) is a large-pore ATP efflux channel with a broad distribution, which allows the exchange of molecules and ions smaller than 1 kDa between the cytoplasm and extracellular space. In this study, we show that in human macrophages PANX1 expression is upregulated by diverse stimuli that promote pyroptosis, which is reminiscent of the previously reported lipopolysaccharide-induced upregulation of PANX1 during inflammasome activation. To further elucidate the function of PANX1, we propose the full-length human Pannexin1 (hPANX1) model through cryo-electron microscopy (cryo-EM) and molecular dynamics (MD) simulation studies, establishing hPANX1 as a homo-heptamer and revealing that both the N-termini and C-termini protrude deeply into the channel pore funnel. MD simulations also elucidate key energetic features governing the channel that lay a foundation to understand the channel gating mechanism. Structural analyses, functional characterizations, and computational studies support the current hPANX1-MD model, suggesting the potential role of hPANX1 in pyroptosis during immune responses.

scholarly journals Cortical and Striatal Electroencephalograms and Apomorphine Effects in the FUS Mouse Model of Amyotrophic Lateral Sclerosis

2021 ◽  
pp. 1-15
Author(s):  
Vasily Vorobyov ◽  
Alexander Deev ◽  
Frank Sengpiel ◽  
Vladimir Nebogatikov ◽  
Aleksey A. Ustyugov
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Motor Neurons ◽  
Cortical Neurons ◽  
Primary Motor Cortex ◽  
Beta Activity ◽  
Systemic Injection ◽  
Eeg Spectra ◽  
Electroencephalogram Eeg ◽  
Lateral Sclerosis

Background: Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motor neurons resulting in muscle atrophy. In contrast to the lower motor neurons, the role of upper (cortical) neurons in ALS is yet unclear. Maturation of locomotor networks is supported by dopaminergic (DA) projections from substantia nigra to the spinal cord and striatum. Objective: To examine the contribution of DA mediation in the striatum-cortex networks in ALS progression. Methods: We studied electroencephalogram (EEG) from striatal putamen (Pt) and primary motor cortex (M1) in ΔFUS(1–359)-transgenic (Tg) mice, a model of ALS. EEG from M1 and Pt were recorded in freely moving young (2-month-old) and older (5-month-old) Tg and non-transgenic (nTg) mice. EEG spectra were analyzed for 30 min before and for 60 min after systemic injection of a DA mimetic, apomorphine (APO), and saline. Results: In young Tg versus nTg mice, baseline EEG spectra in M1 were comparable, whereas in Pt, beta activity in Tg mice was enhanced. In older Tg versus nTg mice, beta dominated in EEG from both M1 and Pt, whereas theta and delta 2 activities were reduced. In younger Tg versus nTg mice, APO increased theta and decreased beta 2 predominantly in M1. In older mice, APO effects in these frequency bands were inversed and accompanied by enhanced delta 2 and attenuated alpha in Tg versus nTg mice. Conclusion: We suggest that revealed EEG modifications in ΔFUS(1–359)-transgenic mice are associated with early alterations in the striatum-cortex interrelations and DA transmission followed by adaptive intracerebral transformations.

scholarly journals Hippocampal Interneurons are Required for Trace Eyeblink Conditioning in Mice

2021 ◽  
Author(s):  
Wei-Wei Zhang ◽  
Rong-Rong Li ◽  
Jie Zhang ◽  
Jie Yan ◽  
Qian-Hui Zhang ◽  
...  
Keyword(s):  
Eyeblink Conditioning ◽  
Pyramidal Cells ◽  
Conditioned Eyeblink ◽  
Cellular Mechanisms ◽  
Sustained Activity ◽  
Early Acquisition ◽  
Freely Moving ◽  
Trace Eyeblink Conditioning

AbstractWhile the hippocampus has been implicated in supporting the association among time-separated events, the underlying cellular mechanisms have not been fully clarified. Here, we combined in vivo multi-channel recording and optogenetics to investigate the activity of hippocampal interneurons in freely-moving mice performing a trace eyeblink conditioning (tEBC) task. We found that the hippocampal interneurons exhibited conditioned stimulus (CS)-evoked sustained activity, which predicted the performance of conditioned eyeblink responses (CRs) in the early acquisition of the tEBC. Consistent with this, greater proportions of hippocampal pyramidal cells showed CS-evoked decreased activity in the early acquisition of the tEBC. Moreover, optogenetic suppression of the sustained activity in hippocampal interneurons severely impaired acquisition of the tEBC. In contrast, suppression of the sustained activity of hippocampal interneurons had no effect on the performance of well-learned CRs. Our findings highlight the role of hippocampal interneurons in the tEBC, and point to a potential cellular mechanism subserving associative learning.

scholarly journals Strengthened Corticosubcortical Functional Connectivity during Muscle Fatigue

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Zhiguo Jiang ◽  
Xiao-Feng Wang ◽  
Guang H. Yue
Keyword(s):  
Motor Control ◽  
Functional Connectivity ◽  
Quantile Regression ◽  
Muscle Fatigue ◽  
Motor Performance ◽  
Primary Motor Cortex ◽  
Motor Task ◽  
Voluntary Contraction ◽  
Control Network ◽  
Subcortical Structures

The present study examined functional connectivity (FC) between functional MRI (fMRI) signals of the primary motor cortex (M1) and each of the three subcortical neural structures, cerebellum (CB), basal ganglia (BG), and thalamus (TL), during muscle fatigue using the quantile regression technique. Understanding activation relation between the subcortical structures and the M1 during prolonged motor performance should help delineate how central motor control network modulates acute perturbations at peripheral sensorimotor system such as muscle fatigue. Ten healthy subjects participated in the study and completed a 20-minute intermittent handgrip motor task at 50% of their maximal voluntary contraction (MVC) level. Quantile regression analyses were carried out to compare the FC between the contralateral (left) M1 and CB, BG, and TL in the minimal (beginning 100 s) versus significant (ending 100 s) fatigue stages. Widespread, statistically significant increases in FC were found in bilateral BG, CB, and TL with the left M1 during significant versus minimal fatigue stages. Our results imply that these subcortical nuclei are critical components in the motor control network and actively involved in modulating voluntary muscle fatigue, possibly, by working together with the M1 to strengthen the descending central command to prolong the motor performance.

Neural Networks and Motor Control

1997 ◽  
Vol 3 (1) ◽  
pp. 52-60 ◽  
Author(s):  
Apostolus P. Georgopoulos
Keyword(s):  
Motor Control ◽  
Spatial Information ◽  
Network Modeling ◽  
Central Place ◽  
Cooperative Interaction ◽  
Neural Network Modeling ◽  
Spinal Motor ◽  
Structural And Functional Properties ◽  
Motor Cortical ◽  
Muscle Activations

Motor control is accomplished by the cooperative interaction of many brain networks, among which the motor cortex holds a central place. This article reviews some of the structural and functional properties of neurons of the motor cortical network, some principles of connectivity with other motor networks, the handling of spatial information regarding reaching movements, and some ideas on how motor cortical commands could be translated to muscle activations by spinal motor networks. Finally, I review recent neural network modeling studies of motor cortical ensemble operations.

scholarly journals Demand on skillfulness modulates interhemispheric inhibition of motor cortices

2016 ◽  
Vol 115 (6) ◽  
pp. 2803-2813 ◽  
Author(s):  
Miles Wischnewski ◽  
Greg M. Kowalski ◽  
Farrah Rink ◽  
Samir R. Belagaje ◽  
Marc W. Haut ◽  
...  
Keyword(s):  
Primary Motor Cortex ◽  
Motor Task ◽  
Conditioning Stimulus ◽  
Motor Evoked Potential ◽  
Inhibitory Effect ◽  
Left Hand ◽  
The Mean ◽  
Small Targets ◽  
Healthy Participants

The role of primary motor cortex (M1) in the control of hand movements is still unclear. Functional magnetic resonance imaging (fMRI) studies of unimanual performance reported a relationship between level of precision of a motor task and additional ipsilateral M1 (iM1) activation. In the present study, we determined whether the demand on accuracy of a movement influences the magnitude of the inhibitory effect between primary motor cortices (IHI). We used transcranial magnetic stimulation (TMS) to measure active IHI (aIHI) of the iM1 on the contralateral M1 (cM1) in the premovement period of a left-hand motor task. Ten healthy participants manipulated a joystick to point to targets of two different sizes. For aIHI, the conditioning stimulus (CS) was applied to iM1, and the test stimulus (TS) to cM1, with an interstimulus interval of 10 ms. The amount of the inhibitory effect of the CS on the motor-evoked potential (MEP) of the subsequent TS was expressed as percentage of the mean MEP amplitude evoked by the single TS. Across different time points of aIHI measurements in the premovement period, there was a significant effect for target size on aIHI. Preparing to point to small targets was associated with weaker aIHI compared with pointing to large targets. The present findings suggest that, during the premovement period, aIHI from iM1 on cM1 is modulated by the demand on accuracy of the motor task. This is consistent with task fMRI findings showing bilateral M1 activation during high-precision movements but only unilateral M1 activity during low-precision movements.

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