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.

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 Neurological Basis of AMP-Dependent Thermoregulation and its Relevance to Central and Peripheral Hyperthermia

2012 ◽  
Vol 33 (2) ◽  
pp. 183-190 ◽  
Author(s):  
Mirko Muzzi ◽  
Francesco Blasi ◽  
Alessio Masi ◽  
Elisabetta Coppi ◽  
Chiara Traini ◽  
...  
Keyword(s):  
Body Temperature ◽  
Preoptic Area ◽  
Febrile Illness ◽  
Electrophysiological Recording ◽  
Spontaneous Firing ◽  
Nucleotidase Activity ◽  
Firing Activity ◽  
Hypothermic Effect ◽  
Adenosine A1

Therapeutic hypothermia is of relevance to treatment of increased body temperature and brain injury, but drugs inducing selective, rapid, and safe cooling in humans are not available. Here, we show that injections of adenosine 5′-monophosphate (AMP), an endogenous nucleotide, promptly triggers hypothermia in mice by directly activating adenosine A1 receptors (A1R) within the preoptic area (POA) of the hypothalamus. Inhibition of constitutive degradation of brain extracellular AMP by targeting ecto 5′-nucleotidase, also suffices to prompt hypothermia in rodents. Accordingly, sensitivity of mice and rats to the hypothermic effect of AMP is inversely related to their hypothalamic 5′-nucleotidase activity. Single-cell electrophysiological recording indicates that AMP reduces spontaneous firing activity of temperature-insensitive neurons of the mouse POA, thereby retuning the hypothalamic thermoregulatory set point towards lower temperatures. Adenosine 5′-monophosphate also suppresses prostaglandin E2-induced fever in mice, having no effects on peripheral hyperthermia triggered by dioxymetamphetamine (ecstasy) overdose. Together, data disclose the role of AMP, 5′-nucleotidase, and A1R in hypothalamic thermoregulation, as well and their therapeutic relevance to treatment of febrile illness.

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.

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.

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 Cortico-subthalamic projections send brief stop signals to halt visually-guided locomotion

2020 ◽  
Author(s):  
Elie M. Adam ◽  
Taylor Johns ◽  
Mriganka Sur
Keyword(s):  
Basal Ganglia ◽  
Motor Cortex ◽  
Subthalamic Nucleus ◽  
Behavioral Strategy ◽  
Visually Guided ◽  
Short Route ◽  
Mesencephalic Locomotor Region ◽  
Neuronal Control ◽  
Control Signals

SummaryGoal-directed locomotion necessitates control signals that propagate from higher-order areas to regulate spinal mechanisms. The cortico-subthalamic hyperdirect pathway offers a short route for cortical information to reach locomotor centers in the brainstem. We developed a task where head-fixed mice run to a visual landmark, then stop and wait to collect reward, and examined the role of secondary motor cortex (M2) projections to the subthalamic nucleus (STN) in controlling locomotion. Our modeled behavioral strategy indicates a switching point in behavior, suggesting a critical neuronal control signal at stop locations. Optogenetic activation of M2 axons in STN leads the animal to stop prematurely. By imaging M2 neurons projecting to STN, we find neurons that are active at the onset of stops, when executed at the landmark but not spontaneously elsewhere. Our results suggest that the M2-STN pathway can be recruited during visually-guided locomotion to rapidly and precisely control the mesencephalic locomotor region through the basal ganglia.

scholarly journals Basal ganglia and cerebellum contributions to vocal emotion processing as revealed by high-resolution fMRI

2021 ◽  
Vol 11 (1) ◽  
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 ◽  
Vocal Emotion ◽  
Variance Explained

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 Effect of Stimulation of Subthalamic Nucleus onbeta Oscillations and Thalamus Tremor Activity in aComputational Model of Parkinson’s Disease  

2020 ◽  
Author(s):  
Seyed-Mojtaba Alavi ◽  
Amin Mirzaei ◽  
Alireza Valizadeh ◽  
Reza Ebrahimpour
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Globus Pallidus ◽  
Subthalamic Nucleus ◽  
Experimental Studies ◽  
Underlying Mechanism ◽  
Motor Deficits ◽  
Synaptic Coupling

Abstract Parkinson’s disease (PD) is associated with abnormal b band oscillations (13-30 Hz) in the cortico-basal ganglia circuits.Abnormally increased striato-pallidal inhibition and strengthening the synaptic coupling between subthalamic nucleus (STN)and globus pallidus externa (GPe), due to the loss of dopamine, are accounted as the potential sources of b oscillations in thebasal ganglia. Deep brain stimulation (DBS) of the basal ganglia subregions is known as a way to reduce the pathological boscillations and motor deficits related to PD. Despite the success of the DBS, its underlying mechanism is poorly understoodand, there is controversy about the inhibitory or excitatory role of the DBS in the literature. Here, we utilized a computationalnetwork model of basal ganglia which consists STN, GPe, globus pallidus interna (GPi), and thalamus neuronal population.This model can capture healthy and pathological b oscillations as what has been observed in experimental studies. Using thismodel, we investigated the effect of DBS to understand whether its effect is excitatory or inhibitory. Our results show that theexcitatory DBS (EDBS) is able to quench the pathological synchrony and b oscillations, while, applying inhibitory DBS (IDBS)failed to quench the PD signs. In addition, the EDBS ameliorated the thalamic activity related to tremor in the model, while,the IDBS outperformed. However, with the help of the model results, we conclude that the effect of the DBS on its target isexcitatory

scholarly journals Subthalamic Nucleus Neurons Differentially Encode Early and Late Aspects of Speech Production

2017 ◽  
Author(s):  
WJ Lipski ◽  
A Alhourani ◽  
T Pirnia ◽  
PW Jones ◽  
C Dastolfo-Hromack ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Firing Rate ◽  
Speech Production ◽  
Subthalamic Nucleus ◽  
Motor Behavior ◽  
Dependent Inhibition ◽  
Subthalamic Neurons ◽  
Intracranial Recording ◽  
Deep Brain Stimulation Surgery

ABSTRACTBasal ganglia-thalamocortical loops mediate all motor behavior, yet little detail is known about the role of basal ganglia nuclei in speech production. Using intracranial recording during deep brain stimulation surgery, we tested the hypothesis that the firing rate of subthalamic nucleus neurons is modulated in response to both planning and motor execution aspects of speech. Nearly half of 79 recorded units exhibited firing rate modulation, during a syllable reading task administered in 12 subjects. Trial-to-trial timing of changes in subthalamic neuronal activity, relative to cue onset versus production onset, revealed that locking to cue presentation was associated more with units that decreased firing rate, while locking to speech onset was associated more with units that increased firing rate. These uniquely acquired data indicate that subthalamic activity is dynamic during the production of speech, reflecting temporally-dependent inhibition and excitation of separate populations of subthalamic neurons.

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