Locomotor pattern generation and descending control: a historical perspective DOI
Réjean Dubuc,

Jean‐Marie Cabelguen,

Dimitri Ryczko

et al.

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

Brainstem Circuits for Locomotion DOI
Roberto Leiras, Jared M. Cregg, Ole Kiehn

et al.

Annual Review of Neuroscience, Journal Year: 2022, Volume and Issue: 45(1), P. 63 - 85

Published: Jan. 5, 2022

Locomotion is a universal motor behavior that expressed as the output of many integrated brain functions. organized at several levels nervous system, with brainstem circuits acting gate between areas regulating innate, emotional, or motivational locomotion and executive spinal circuits. Here we review recent advances on involved in controlling locomotion. We describe how delineated command govern start, speed, stop, steering also discuss these pathways interface cord diverse important for context-specific selection A recurrent theme need to establish functional connectome from Finally, point unresolved issues concerning function locomotor control.

Language: Английский

Citations

93
Basal ganglia–spinal cord pathway that commands locomotor gait asymmetries in mice DOI Creative Commons
Jared M. Cregg, Simrandeep Kaur Sidhu, Roberto Leiras

et al.

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(4), P. 716 - 727

Published: Feb. 12, 2024

Abstract The basal ganglia are essential for executing motor actions. How the engage spinal networks has remained elusive. Medullary Chx10 gigantocellular (Gi) neurons required turning gait programs, suggesting that gaits organized by executed via this descending pathway. Performing deep brainstem recordings of Gi Ca 2+ activity in adult mice, we show striatal projection initiate a dominant crossed pathway to on contralateral side. Using intersectional viral tracing and cell-type-specific modulation, uncover principal ganglia–spinal cord locomotor asymmetries mice: → pontine reticular nucleus, oral part (PnO) cord. Modulating restricted PnO restores competence upon damage, dysfunction may contribute debilitating deficits observed Parkinson’s disease. Our results reveal stratified circuit architecture underlying critical program.

Language: Английский

Citations

21
Muscarinic acetylcholine receptors for psychotic disorders: bench-side to clinic DOI Creative Commons
Samantha E. Yohn, Peter J. Weiden, Christian C. Felder

et al.

Trends in Pharmacological Sciences, Journal Year: 2022, Volume and Issue: 43(12), P. 1098 - 1112

Published: Oct. 20, 2022

Modern interest in muscarinic acetylcholine receptor (mAChR) activators for schizophrenia began the 1990s when xanomeline, an M1/M4-preferring mAChR agonist developed cognitive symptoms of Alzheimer's disease (AD), had unexpected antipsychotic activity. However, strategies to address tolerability concerns associated with activation peripheral mAChRs were not available at that time. The discovery specific targeted ligands and combination treatments reduce engagement have advanced potential as effective psychotic disorders. This review provides perspectives on background identification antipsychotics, advances preclinical understanding targets, current state under active clinical development schizophrenia.

Language: Английский

Citations

65
Optogenetic stimulation of glutamatergic neurons in the cuneiform nucleus controls locomotion in a mouse model of Parkinson’s disease DOI Open Access

Maxime Fougère,

Cornelis Immanuel van der Zouwen,

Joël Boutin

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2021, Volume and Issue: 118(43)

Published: Oct. 20, 2021

In Parkinson's disease (PD), the loss of midbrain dopaminergic cells results in severe locomotor deficits, such as gait freezing and akinesia. Growing evidence indicates that these deficits can be attributed to decreased activity mesencephalic region (MLR), a brainstem controlling locomotion. Clinicians are exploring deep brain stimulation MLR treatment option improve function. The variable, from modest promising. However, within MLR, clinicians have targeted pedunculopontine nucleus exclusively, while leaving cuneiform unexplored. To our knowledge, effects never been determined parkinsonian conditions any animal model. Here, we addressed this issue mouse model PD, based on bilateral striatal injection 6-hydroxydopamine, which damaged nigrostriatal pathway activity. We show selective optogenetic glutamatergic neurons mice expressing channelrhodopsin Cre-dependent manner Vglut2-positive (Vglut2-ChR2-EYFP mice) increased number initiations, time spent locomotion, controlled speed. Using learning-based movement analysis, found limb kinematics optogenetic-evoked locomotion pathological were largely similar those recorded intact animals. Our work identifies potentially clinically relevant target conditions. study should open avenues develop using stimulation, pharmacotherapy, or optogenetics.

Language: Английский

Citations

57
Targeted activation of midbrain neurons restores locomotor function in mouse models of parkinsonism DOI Creative Commons
Débora Masini, Ole Kiehn

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Jan. 26, 2022

Abstract The pedunculopontine nucleus (PPN) is a locomotor command area containing glutamatergic neurons that control initiation and maintenance. These motor actions are deficient in Parkinson’s disease (PD), where dopaminergic neurodegeneration alters basal ganglia activity. Being downstream of the ganglia, PPN may be suitable target for ameliorating parkinsonian symptoms. Here, we use vivo cell-type specific activation to restore function two mouse models parkinsonism made by acute pharmacological blockage dopamine transmission. With combination chemo- opto-genetics, show excitation caudal can normalize otherwise severe deficit PD, whereas targeting local GABAergic population only leads recovery slow locomotion. rescue driven independent activity nearby promoting Cuneiform neurons. Our observations point as potential neuromodulatory restoration PD.

Language: Английский

Citations

55
Re-examining the pathobiological basis of gait dysfunction in Parkinson’s disease DOI
Newton Cho, Lorraine V. Kalia, Suneil K. Kalia

et al.

Trends in Neurosciences, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

1
Pedunculopontine Chx10+ neurons control global motor arrest in mice DOI Creative Commons
Haizea Goñi-Erro, Raghavendra Selvan, Vittorio Caggiano

et al.

Nature Neuroscience, Journal Year: 2023, Volume and Issue: 26(9), P. 1516 - 1528

Published: July 27, 2023

Abstract Arrest of ongoing movements is an integral part executing motor programs. Behavioral arrest may happen upon termination a variety goal-directed or as global either in the context fear response to salient environmental cues. The neuronal circuits that bridge with executive implement are poorly understood. We report discovery activation glutamatergic Chx10-derived neurons pedunculopontine nucleus (PPN) mice arrests all while simultaneously causing apnea and bradycardia. This has pause-and-play pattern instantaneous interruption movement followed by short-latency continuation from where it was paused. Mice naturally perform bouts same combination autonomic features. Chx10-PPN-evoked different ventrolateral periaqueductal gray-induced freezing. Our study defines command induces arrest, which be recruited cues allow for preparatory arousal state, identifies locomotor-opposing role rostrally biased PPN.

Language: Английский

Citations

21
Freezing of Gait in Parkinson’s Disease: Invasive and Noninvasive Neuromodulation DOI
Shervin Rahimpour, Wendy Gaztanaga, Amol P. Yadav

et al.

Neuromodulation Technology at the Neural Interface, Journal Year: 2020, Volume and Issue: 24(5), P. 829 - 842

Published: Dec. 26, 2020

Language: Английский

Citations

42
The Mesencephalic Locomotor Region: Beyond Locomotor Control DOI Creative Commons
Brian R. Noga, Patrick J. Whelan

Frontiers in Neural Circuits, Journal Year: 2022, Volume and Issue: 16

Published: May 9, 2022

The mesencephalic locomotor region (MLR) was discovered several decades ago in the cat. It functionally defined based on ability of low threshold electrical stimuli within a comprising cuneiform and pedunculopontine nucleus to evoke locomotion. Since then, similar regions have been found diverse vertebrate species, including lamprey, skate, rodent, pig, monkey, human. MLR, while often viewed under lens locomotion, is involved processes involving autonomic nervous system, respiratory state-dependent activation motor systems. This review will discuss that comprises MLR examine their respective connectomes from both an anatomical functional angle. From perspective, primes cardiovascular systems before activity occurs. Inputs variety higher structures, direct outputs monoaminergic nuclei, allow be able respond appropriately These effects are roughly divided into escape exploratory behavior, also can reinforce selection these behaviors through projections adjacent structures such as periaqueductal gray or limbic cortical regions. Findings rat, mouse, cat discussed highlight similarities differences among species.

Language: Английский

Citations

28
The PPN and motor control: Preclinical studies to deep brain stimulation for Parkinson’s disease DOI Creative Commons

Caixia Lin,

Margreet C. Ridder, Pankaj Sah

et al.

Frontiers in Neural Circuits, Journal Year: 2023, Volume and Issue: 17

Published: Feb. 28, 2023

The pedunculopontine nucleus (PPN) is the major part of mesencephalic locomotor region, involved in control gait and locomotion. PPN contains glutamatergic, cholinergic, GABAergic neurons that all make local connections, but also have long-range ascending descending connections. While initially thought as a region only locomotion, recent evidence showing this structure participates decision-making to initiate movement. Clinically, has been used target for deep brain stimulation manage freezing late Parkinson’s disease. In review, we will discuss current thinking on role control. We focus cytoarchitecture functional connectivity relationship motor

Language: Английский

Citations

14