A permissive role for dopamine in the production of vigorous movements

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Nov. 3, 2022

Abstract Dopamine is essential for the production of vigorous movements, but how dopamine modifies gain motor commands remains unclear. Here, we developed a dexterous task in which head-restrained mice self-initiate fast and large-amplitude lever pushes with their left forelimb to earn rewards. We show that this goal-directed depends on cortico-striatal circuits hemisphere contralateral limb used push lever. find unilateral loss midbrain neurons reduces speed amplitude pushes, levodopa treatment rapidly restores vigor, consistent parkinsonian bradykinesia. Photometry recordings striatal levels indicate therapeutic efficacy does not require phasic release. In dopamine-intact mice, optogenetic stimulation calibrated mimic transients evoked by rewards also insufficient increase movements. Together, our data are unlikely specify vigor movements online as they being executed, suggest instead plays permissive role selection Our findings have important implications understanding basal ganglia contribute control under physiological conditions Parkinson’s disease.

Language: Английский

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Rat models of major neurodegenerative disorders

Ageing and Neurodegenerative Diseases, Journal Year: 2022, Volume and Issue: 2(4), P. 17 - 17

Published: Jan. 1, 2022

No single animal model can recapitulate all the features of a particular human disease on its own. Historically, rats have been used to study neurobiology and underlying functional networks. Likewise, rat models created neurodegenerative mechanisms therapeutic interventions. In last decades, shift towards use mice has observed in many research fields, not least because comparatively easier genetic manipulation mice. However, with full sequence genome being available, advances rat, advanced test regimens biomarkers at hand, presents itself once more as valuable organism for studying disorders. This review provides an overview currently well-characterized Alzheimer’s disease, Parkinson’s Huntington’s well their advantages disorders evaluating

Language: Английский

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Parkinson Disease Recognition Using a Gamified Website: Machine Learning Development and Usability Study

JMIR Formative Research, Journal Year: 2023, Volume and Issue: 7, P. e49898 - e49898

Published: Sept. 4, 2023

Parkinson disease (PD) affects millions globally, causing motor function impairments. Early detection is vital, and diverse data sources aid diagnosis. We focus on lower arm movements during keyboard trackpad or touchscreen interactions, which serve as reliable indicators of PD. Previous works explore tapping unstructured device monitoring; we attempt to further these with structured tests taking into account 2D hand movement in addition finger tapping. Our feasibility study uses keystroke mouse from a remotely conducted, structured, web-based test combined self-reported PD status create predictive model for detecting the presence

Language: Английский

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Regulation of N-type calcium channels by nociceptin receptors and its possible role in neurological disorders

Molecular Brain, Journal Year: 2022, Volume and Issue: 15(1)

Published: Nov. 24, 2022

Abstract Activation of nociceptin opioid peptide receptors (NOP, a.k.a. opioid-like receptor-1, ORL-1) by the ligand nociceptin/orphanin FQ, leads to G protein-dependent regulation Cav2.2 (N-type) voltage-gated calcium channels (VGCCs). This typically causes a reduction in currents, triggering changes presynaptic levels and thus neurotransmission. Because widespread expression patterns NOP VGCCs across multiple brain regions, dorsal horn spinal cord, root ganglia, this results alteration numerous neurophysiological features. Here we review N-type NOP-nociceptin system context neurological conditions such as anxiety, addiction, pain.

Language: Английский

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Striatal dopamine contributions to skilled motor learning

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 7, 2024

Abstract Coordinated multi-joint limb and digit movements - “manual dexterity” underlie both specialized skills (e.g., playing the piano) more mundane tasks tying shoelaces). Impairments in dexterous skill cause significant disability, as occurs with motor cortical injury, Parkinson’s Disease, a range of other pathologies. Clinical observations, well basic investigations, suggest that cortico-striatal circuits play critical role learning performing skills. Furthermore, dopaminergic signaling these regions is implicated synaptic plasticity learning. Nonetheless, striatal dopamine skilled remains poorly understood. Here, we use fiber photometry paired genetically encoded sensor to investigate release mice learn perform reaching task. Dopamine rapidly increases during reach peaks near pellet consumption. In dorsolateral striatum, dynamics are faster than dorsomedial ventral striatum. Across training, performance improves, shifts from consumption cues predict availability, particularly medial areas prediction errors present across reduced after an unsuccessful reach. These findings show behaviors change differentially regulated subregions.

Language: Английский

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Dopamine Receptor-Expressing Neurons Are Differently Distributed throughout Layers of the Motor Cortex to Control Dexterity

eNeuro, Journal Year: 2024, Volume and Issue: 11(3), P. ENEURO.0490 - 23.2023

Published: Feb. 29, 2024

The motor cortex comprises the primary descending circuits for flexible control of voluntary movements and is critically involved in skill learning. Motor learning impaired patients with Parkinson's disease, but precise mechanisms are still not well understood. Here we have used transgenic mice, electrophysiology, situ hybridization, neural tract-tracing methods to target genetically defined cell types expressing D1 D2 dopamine receptors cortex. We observed that putative receptor-expressing neurons (D1+ D2+, respectively) organized highly segregated, nonoverlapping populations. Moreover, based on ex vivo patch-clamp recordings, showed D1+ D2+ cells distinct morphological electrophysiological properties. Finally, chemogenetic inhibition D1+, disrupts skilled forelimb reaching adult mice. Overall, these results demonstrate segregated play a specialized role manual dexterity.

Language: Английский

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Motor-Control Notions in Health and Disease (What Controls Motor Control?)

Published: March 29, 2024

The term `motor control´ encompasses a wide range of mechanisms thought to be implicated in the organization movements. Their study, like that any other scientific field, must use specific notions get grips with them. This review is therefore organized along series are frequently used motor control, and we will discuss them particular emphasis on neurological conditions, which may disrupt normal functioning. We start short description roles space time, movements take place. Subsequently deal kinematics kinetics (dynamics) Then, list inputs motoneurons (MNs), which, different forms, convey signals from central nervous system (CNS) skeletal muscles muscle spindles, including pattern generators (CPGs), sensory supraspinal descending fiber systems. Some helpers movement introduced, such as internal models neuronal network models. A relatively brief section sensory-motor learning follow because abilities required endow flexibility adaptability. major placed processes, result genetic modifications, autoimmune diseases, neurodegenerative infections well vascular traumatic lesions. These diseases lead variety impairments symptoms, particularly derangements cerebellar ataxia, spasticity, (other) disorders Parkinson’s syndromes. conclusion there no unique top controller controls ´motor control`.

Language: Английский

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Fair and Accessible Parkinson’s Disease Screening using a Machine Learning-Powered Web Platform: Research Protocol and Preliminary Results

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 17, 2024

Abstract Digital technologies offer unprecedented opportunities to screen for conditions like Parkinson’s Disease (PD) in a scalable and accessible manner. With the widespread adoption of smartphones computers, general public is constantly interacting with digital interfaces, leaving behind wealth data that can be harnessed health screening. Keystroke dynamics, touchscreen interactions, other footprints have emerged as potential indicators PD. By analyzing patterns keyboard typing, gestures, indicators, it now possible detect subtle motor impairments associated We propose further develop, refine, validate baseline predictive model disease based on keystroke measurements which we developed tested participants Hawaii. Through extensive experimentation, project aims determine optimal combination features yield highest sensitivity specificity distinguishing without PD while algorithmically reducing disparities performance across race socioeconomic status. A central challenge this research will ensuring fairness by mitigating biases caused differences laptop desktop dimensions, mouse responsiveness, configurations. These are likely vary status, requiring thorough analysis these employment algorithmic techniques mitigate underlying problem. Additionally, conduct human-centered design sessions understand how create such screening tools manner sensitive Indigenous sovereignty. Our findings underscore leveraging technology-measured limb movement reliable method early detection This holds promise individuals who may potentially affected earlier an manner, thus related diagnosis.

Language: Английский

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Sensorimotor functioning changes in response to global exercise versus handwriting upper limb exercise training in Parkinson’s disease, results from a phase II randomised controlled trial

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(8), P. e0309217 - e0309217

Published: Aug. 29, 2024

People with Parkinson's disease (PwPD) present motor alterations which can impact daily life tasks that require speed and/or accuracy of movement.

Language: Английский

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Learning-related oscillatory dynamics in the human cortico-basal ganglia network during motor sequence initiation in Parkinson’s Disease

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 15, 2024

ABSTRACT Learning dexterous motor sequences is crucial to autonomy and quality of life but can be altered in Parkinson’s Disease (PD). involves optimizing pre-movement planning (preplanning) multiple sequence elements reduce computational overhead during active movement. However, it unclear which brain regions mediate preplanning or how this process evolves with learning. Recording cortico-basal ganglia field potentials a multi-day typing task four individuals PD, we found evidence for network-wide multi-element that improved learning, facilitated by functional connectivity. In both cortex basal ganglia, gamma (γ, 30–250 Hz) activity, historically linked population spiking, distinguished between future action became increasingly predictive For γ, increase was tied learning-related cross-frequency coupling led cortically-driven network delta (δ, 0.5–4 synchrony. More generally, coordinated δ supported complex pattern learning-driven couplings within including striatal lead cortical beta (β, 12–30 reflecting the specialized roles these preparation. contrast, impaired learning characterized practice-driven decreases γ’s value, limited absent synchrony, dynamics possibly pathologically high inter-basal These results suggest cortically-led phase coordination optimized through enhanced recruitment higher-frequency neural activity. Neurostimulation enhances synchrony may thus hold potential improving skilled fine control PD.

Language: Английский

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