scholarly journals Optogenetic investigation into the role of the subthalamic nucleus in motor control

2020 ◽  
Author(s):  
Adriane Guillaumin ◽  
Gian Pietro Serra ◽  
François Georges ◽  
Åsa Wallén-Mackenzie
Keyword(s):  
Motor Control ◽  
Basal Ganglia ◽  
Experimental Evidence ◽  
Subthalamic Nucleus ◽  
Motor Coordination ◽  
List Type ◽  
Motor Tasks ◽  
Experimental Support ◽  
Freely Moving

AbstractThe subthalamic nucleus is important achieve intended movements. Loss of its normal function is strongly associated with several movement disorders. Classical basal ganglia models postulate that two parallel pathways, the direct and indirect pathways, exert opposing control over movement, with the subthalamic nucleus part of the indirect pathway through which competing motor programs are prevented. The subthalamic nucleus is regulated by both inhibitory and excitatory projections but experimental evidence for its role in motor control has remained sparse. The objective here was to tease out the selective impact of the subthalamic nucleus on several motor parameters required to achieve intended movement, including locomotion, balance and motor coordination. Optogenetic excitation and inhibition using both bilateral and unilateral stimulations of the subthalamic nucleus were implemented in freely-moving mice. The results demonstrate that selective optogenetic inhibition of the subthalamic nucleus enhances locomotion while its excitation reduces locomotion. These findings lend experimental support to basal ganglia models in terms of locomotion. However, further analysis of subthalamic nucleus excitation revealed grooming and disturbed gait. Selective excitation also caused reduced motor coordination, independent of grooming, in advanced motor tasks. This study contributes experimental evidence for a regulatory role of the subthalamic nucleus in motor control.HighlightsBilateral optogenetic excitation of the subthalamic nucleus in freely-moving mice reduces forward locomotion while optogenetic inhibition leads to its increase.Unilateral optogenetic excitation and inhibition of the subthalamic nucleus cause opposite rotational behavior.Bilateral optogenetic excitation, but not inhibition, of the subthalamic nucleus induces jumping and self-grooming behavior.Engaged in advanced motor tasks, bilateral optogenetic excitation causes mice to lose motor coordination.The results provide experimental support for predictions by the basal ganglia motor model on the role of the subthalamic nucleus in locomotion, and identifies a causal role for the subthalamic nucleus in self-grooming.

scholarly journals Cerebellar Dysfunction in Adults with Prader Willi Syndrome

2021 ◽  
Vol 10 (15) ◽  
pp. 3320
Author(s):  
Laura Blanco-Hinojo ◽  
Laia Casamitjana ◽  
Jesus Pujol ◽  
Gerard Martínez-Vilavella ◽  
Susanna Esteba-Castillo ◽  
...  
Keyword(s):  
Motor Control ◽  
Motor Function ◽  
Motor Coordination ◽  
Task Demands ◽  
Functional Mobility ◽  
Prader Willi Syndrome ◽  
Pathophysiological Mechanism ◽  
Motor Tasks ◽  
Correlation Pattern ◽  
Motor Processing

Severe hypotonia during infancy is a hallmark feature of Prader Willi syndrome (PWS). Despite its transient expression, moto development is delayed and deficiencies in motor coordination are present at older ages, with no clear pathophysiological mechanism yet identified. The diverse motor coordination symptoms present in adult PWS patients could be, in part, the result of a common alteration(s) in basic motor control systems. We aimed to examine the motor system in PWS using functional MRI (fMRI) during motor challenge. Twenty-three adults with PWS and 22 matched healthy subjects participated in the study. fMRI testing involved three hand motor tasks of different complexity. Additional behavioral measurements of motor function were obtained by evaluating hand grip strength, functional mobility, and balance. Whole brain activation maps were compared between groups and correlated with behavioral measurements. Performance of the motor tasks in PWS engaged the neural elements typically involved in motor processing. While our data showed no group differences in the simplest task, increasing task demands evoked significantly weaker activation in patients in the cerebellum. Significant interaction between group and correlation pattern with measures of motor function were also observed. Our study provides novel insights into the neural substrates of motor control in PWS by demonstrating reduced cerebellar activation during movement coordination.

scholarly journals The Subthalamic Nucleus: Unravelling New Roles and Mechanisms in the Control of Action

2018 ◽  
Vol 25 (1) ◽  
pp. 48-64 ◽  
Author(s):  
Tora Bonnevie ◽  
Kareem A. Zaghloul
Keyword(s):  
Deep Brain Stimulation ◽  
Basal Ganglia ◽  
Subthalamic Nucleus ◽  
Action Control ◽  
Brain Disorders ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
High Level ◽  
Deep Brain

How do we decide what we do? This is the essence of action control, the process of selecting the most appropriate response among multiple possible choices. Suboptimal action control can involve a failure to initiate or adapt actions, or conversely it can involve making actions impulsively. There has been an increasing focus on the specific role of the subthalamic nucleus (STN) in action control. This has been fueled by the clinical relevance of this basal ganglia nucleus as a target for deep brain stimulation (DBS), primarily in Parkinson’s disease but also in obsessive-compulsive disorder. The context of DBS has opened windows to study STN function in ways that link neuroscientific and clinical fields closely together, contributing to an exceptionally high level of two-way translation. In this review, we first outline the role of the STN in both motor and nonmotor action control, and then discuss how these functions might be implemented by neuronal activity in the STN. Gaining a better understanding of these topics will not only provide important insights into the neurophysiology of action control but also the pathophysiological mechanisms relevant for several brain disorders and their therapies.

scholarly journals Basal ganglia and cerebellar contributions to vocal emotion processing: a high resolution fMRI study

2020 ◽  
Author(s):  
Leonardo Ceravolo ◽  
Sascha Frühholz ◽  
Jordan Pierce ◽  
Didier Grandjean ◽  
Julie Péron
Keyword(s):  
Basal Ganglia ◽  
High Resolution ◽  
Globus Pallidus ◽  
Subthalamic Nucleus ◽  
Effective Connectivity ◽  
Emotion Processing ◽  
Brain Regions ◽  
Fmri Study ◽  
Vocal Emotion

AbstractUntil recently, brain networks underlying emotional voice prosody decoding and processing were focused on modulations in primary and secondary auditory, ventral frontal and prefrontal cortices, and the amygdala. Growing interest for a specific role of the basal ganglia and cerebellum was recently brought into the spotlight. In the present study, we aimed at characterizing the role of such subcortical brain regions in vocal emotion processing, at the level of both brain activation and functional and effective connectivity, using high resolution functional magnetic resonance imaging. Variance explained by low-level acoustic parameters (fundamental frequency, voice energy) was also modelled. Wholebrain data revealed expected contributions of the temporal and frontal cortices, basal ganglia and cerebellum to vocal emotion processing, while functional connectivity analyses highlighted correlations between basal ganglia and cerebellum, especially for angry voices. Seed-to-seed and seed-to-voxel effective connectivity revealed direct connections within the basal ganglia ̶ especially between the putamen and external globus pallidus ̶ and between the subthalamic nucleus and the cerebellum. Our results speak in favour of crucial contributions of the basal ganglia, especially the putamen, external globus pallidus and subthalamic nucleus, and several cerebellar lobules and nuclei for an efficient decoding of and response to vocal emotions.

scholarly journals Cortico-basal-ganglia communication: Temporally structured activity for selective motor control

2018 ◽  
Author(s):  
Petra Fischer ◽  
Witold Lipski ◽  
Wolf-Julian Neumann ◽  
Robert Sterling Turner ◽  
Pascal Fries ◽  
...  
Keyword(s):  
Motor Control ◽  
Basal Ganglia ◽  
Firing Rate ◽  
Structural Connectivity ◽  
Reaction Times ◽  
Spike Timing ◽  
List Type ◽  
Gamma Phase ◽  
Neural Pathways ◽  
Phase Coupling

AbstractDespite the hard-wired structural connectivity of neural pathways, neural circuits allow context-dependent reactions to sensory cues by triggering the desired movement. Cortico-basal-ganglia circuits seem particularly important for flexible motor control as this is impaired in Parkinson’s disease (PD). We analysed subthalamic nucleus (STN) spike and cortical ECoG activity from PD patients performing a visually-cued hand grip task. Fast reaction times were preceded by enhanced STN spike-to-cortical gamma phase coupling irrespective of firing rate changes, suggesting a role of gamma coupling in motor preparation. STN spike timing was offset by half a cycle when comparing ipsilateral with contralateral movements. Additionally, cortical high-frequency activity increased more steeply within each gamma cycle at the sites that showed the strongest coupling with STN spikes. Cortico-basal-ganglia gamma coupling may thus help shape neural activity to facilitate selective motor control. The observation that this effect occurs independent of changes in mean firing rate has far-reaching implications.HighlightsFast RTs were preceded by enhanced STN spike-to-cortical gamma phase couplingSTN spike probability was significantly modulated relative to the gamma cycleDuring ipsilateral movement, spikes were more likely at the opposite part of the cycleSTN output may thus help shape cortical gamma for selective motor control

Understanding Parkinsonian Handwriting Through a Computational Model of Basal Ganglia

2008 ◽  
Vol 20 (10) ◽  
pp. 2491-2525 ◽  
Author(s):  
Garipelli Gangadhar ◽  
Denny Joseph ◽  
V. Srinivasa Chakravarthy
Keyword(s):  
Basal Ganglia ◽  
Computational Model ◽  
Globus Pallidus ◽  
Subthalamic Nucleus ◽  
Line Contour ◽  
Velocity Fluctuations ◽  
Signaling Model ◽  
Tip Velocity ◽  
Handwriting Generation

Handwriting in Parkinson's disease (PD) is typically characterized by micrographia, jagged line contour, and unusual fluctuations in pen tip velocity. Although PD handwriting features have been used for diagnostics, they are not based on a signaling model of basal ganglia (BG). In this letter, we present a computational model of handwriting generation that highlights the role of BG. When PD conditions like reduced dopamine and altered dynamics of the subthalamic nucleus and globus pallidus externa subsystems are simulated, the handwriting produced by the model manifested characteristic PD handwriting distortions like micrographia and velocity fluctuations. Our approach to PD modeling is in tune with the perspective that PD is a dynamic disease.

Role of Ionotropic Glutamatergic and GABAergic Inputs on the Firing Activity of Neurons in the External Pallidum in Awake Monkeys

2004 ◽  
Vol 92 (5) ◽  
pp. 3069-3084 ◽  
Author(s):  
H. Kita ◽  
A. Nambu ◽  
K. Kaneda ◽  
Y. Tachibana ◽  
M. Takada
Keyword(s):  
Basal Ganglia ◽  
Subthalamic Nucleus ◽  
Nmda Antagonist ◽  
Spontaneous Firing ◽  
Firing Activity ◽  
Combined Application ◽  
Local Injections ◽  
High Level ◽  
Spontaneous Firing Rate

The neurons in the external segment of the pallidum (GPe) in awake animals maintain a high level of firing activity. The level and pattern of the activity change with the development of basal ganglia disorders including parkinsonism and hemiballism. The GPe projects to most of the nuclei in the basal ganglia. Thus exploring the mechanisms controlling the firing activity is essential for understanding basal ganglia function in normal and pathological conditions. To explore the role of ionotropic glutamatergic and GABAergic inputs to the GPe, unit recordings combined with local injections of receptor antagonists were performed in awake monkeys. Observations on the effects of local application of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate antagonist 1,2,3,4-tetrahydro-6-nitro-2, 3-dioxo-benzo[f]quinoxaline-7-sulfonamide, the N-methyl-d-aspartic acid (NMDA) antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid, and the GABAA antagonist gabazine as well as the effects of muscimol blockade of the subthalamic nucleus on the spontaneous firing rate, firing patterns, and cortical stimulation induced responses in the GPe suggested the following: sustained glutamatergic and GABAergic inputs control the level of the spontaneous firing of GPe neurons; both AMPA/kainate and NMDA receptors are activated by glutamatergic inputs; some GPe neurons receive glutamatergic inputs originating from areas other than the subthalamic nucleus; no GPe neurons became silent after a combined application of glutamate and GABA antagonists, suggesting that GPe neurons have intrinsic properties or nonionotropic glutamatergic tonic inputs that sustain a fast oscillatory firing or a combination of a fast and a slow oscillatory firing in GPe neurons.

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