Abnormal activity in the brainstem affects gait in a neuromusculoskeletal model

Journal of NeuroEngineering and Rehabilitation, Journal Year: 2025, Volume and Issue: 22(1)

Published: April 4, 2025

Abstract Background The ability to start and stop locomotion in response different situations is an essential survival strategy mammals. Mammalian controlled by central pattern generators the spinal cord, which are modulated higher centers, particularly stimulation of midbrain locomotor region. region consists pedunculopontine nucleus cuneiform nucleus, each having roles animals. Optogenetic activation increases activities, whereas that decreases them. In neurological disorders such as Parkinson’s disease, patients exhibit disturbed controls, including freezing gait, defined “a brief, episodic absence or marked reduction forward progression feet despite intention walk.” However, details pathophysiological mechanisms gait remain unclear. Methods this study, we aimed elucidate underlying using a two-dimensional neuromusculoskeletal model fixed on sagittal plane. This consisted body with seven links 18 muscles well neural system brainstem cord. We developed normal condition then derived abnormal activity modifying parameters during initial 3 s walking. Results models walked successfully following internal parameter optimization standard genetic algorithms. model, 156 events were detected among 40,000 sets gait-identifying algorithm. Hierarchical cluster analysis identified four clusters parameters, based intensities activity, differentiated physiological movement types similar clinical classification gait. Conclusions Our results indicate activities could be linked modifications those generate observed subtypes. can provide insights relevant for understanding expected assist

Language: Английский

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Cholinergic Modulation of Locomotor Circuits in Vertebrates

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(18), P. 10738 - 10738

Published: Sept. 14, 2022

Locomotion is a basic motor act essential for survival. Amongst other things, it allows animals to move in their environment seek food, escape predators, or mates reproduction. The neural mechanisms involved the control of locomotion have been examined many vertebrate species and clearer picture progressively emerging. muscle synergies responsible propulsion are generated by networks located spinal cord. In turn, descending supraspinal inputs starting, maintaining, stopping as well steering controlling speed. Several neurotransmitter systems play crucial role modulating activity during locomotion. For instance, cholinergic both at levels underlying focus present review. Much information gained on modulation was obtained from lamprey model. Nicotinic increase level excitation brainstem command neurons, reticulospinal neurons (RSNs), whereas muscarinic activate select group hindbrain that project RSNs boost excitation. Muscarinic also reduce transmission sensory brainstem, phenomenon could help sustaining goal directed cord, intrinsic strongly modulate interneurons motoneurons locomotor output. Altogether, review underlines importance vertebrates.

Language: Английский

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The Mesoscopic Connectome of the Cholinergic Pontomesencephalic Tegmentum

Frontiers in Neuroanatomy, Journal Year: 2022, Volume and Issue: 16

Published: May 17, 2022

The pontomesencephalic tegmentum, comprising the pedunculopontine nucleus and laterodorsal tegmental nucleus, is involved in various functions via complex connections; however, organizational structure of these circuits whole brain not entirely clear. Here, combining viral tracing with fluorescent micro-optical sectional tomography, we comprehensively investigated input output two cholinergic subregions a continuous whole-brain dataset. We found that nuclei receive abundant similar spatial distributions but different quantitative measures acquire neuromodulatory afferents from ascending reticular activation system. Meanwhile, project to targeting areas throughout multiple regions have preferences 3D. Moreover, some connections are unidirectional, including projections ventral posterior thalamus, impacts on locomotion anxiety. These results reveal integrated connectome midbrain, thus improving present understanding pontine-tegmental system its anatomical functional modulation.

Language: Английский

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The Mesencephalic Locomotor Region: Multiple Cell Types, Multiple Behavioral Roles, and Multiple Implications for Disease

The Neuroscientist, Journal Year: 2022, Volume and Issue: 30(3), P. 347 - 366

Published: Dec. 28, 2022

The mesencephalic locomotor region (MLR) controls locomotion in vertebrates. In humans with Parkinson disease, deficits are increasingly associated decreased activity the MLR. This brainstem region, commonly considered to include cuneiform and pedunculopontine nuclei, has been explored as a target for deep brain stimulation improve function, but results variable, from modest promising. However, MLR is heterogeneous structure, identification of best cell type only beginning. Here, I review studies that uncovered role genetically defined types, highlight cells whose activation improves function animal models disease. promising types activate comprise some glutamatergic neurons caudal well cholinergic nucleus. Activation GABAergic should be avoided, since they stop or evoke bouts flanked numerous stops. also potential spinal cord injury, supranuclear palsy, primary progressive freezing gait, stroke. Better targeting achieved through optimized protocols, pharmacotherapy, development optogenetics human use.

Language: Английский

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Locomotor pattern generation and descending control: a historical perspective

Journal of Neurophysiology, Journal Year: 2023, Volume and Issue: 130(2), P. 401 - 416

Published: July 19, 2023

The ability to generate and control locomotor movements depends on complex interactions between many areas of the nervous system, musculoskeletal environment. How system manages accomplish this task has been subject investigation for more than a century. In vertebrates, locomotion is generated by neural networks located in spinal cord referred as central pattern generators. Descending inputs from brain stem initiate, maintain, stop well speed direction. Sensory adapt programs environmental conditions. This review presents comparative historical overview some mechanisms underlying vertebrates. We have put an emphasis descending control.

Language: Английский

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