Dopamine Pumping Up Spinal Locomotor Network Function

Sharples, Simon A.

doi:10.1523/jneurosci.0019-17.2017

Cited by 4 publications

(3 citation statements)

References 30 publications

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“…However, the A11 projects to the spinal cord (Commissiong and Sedgwick, 1975 ; Skagerberg and Lindvall, 1985 ; Holstege et al, 1996 ; Koblinger et al, 2014 ; review Sharples et al, 2014 ) and has known roles in pain modulation (Charbit et al, 2009 ) and motor control (Ondo et al, 2000 ; Clemens et al, 2006 ; Qu et al, 2007 ). It has also been shown that dopamine modulates mammalian spinal CPG networks (Barrière et al, 2004 ; Humphreys and Whelan, 2012 ; Sharples et al, 2015 ; Picton et al, 2017 ; Sharples, 2017 ; Sharples and Whelan, 2017 ). These data support a possibility for a descending dopamine system in mammalian locomotor control.…”

Section: The Diencephalon: a Hub For Goal-directed Locomotionmentioning

confidence: 99%

Integration of Descending Command Systems for the Generation of Context-Specific Locomotor Behaviors

et al. 2017

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Over the past decade there has been a renaissance in our understanding of spinal cord circuits; new technologies are beginning to provide key insights into descending circuits which project onto spinal cord central pattern generators. By integrating work from both the locomotor and animal behavioral fields, we can now examine context-specific control of locomotion, with an emphasis on descending modulation arising from various regions of the brainstem. Here we examine approach and avoidance behaviors and the circuits that lead to the production and arrest of locomotion.

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Section: The Diencephalon: a Hub For Goal-directed Locomotionmentioning

confidence: 99%

Integration of Descending Command Systems for the Generation of Context-Specific Locomotor Behaviors

et al. 2017

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“…Increasing oxotremorine up to 100 μM seemed to become less effective as the induced motor activity exhibited an increased period, compared to that with 5 and 10 μM oxotremorine ( Fig 2B ), and a disorganized motor burst expression ( Fig 2D ). The various patterns elicited when raising the oxotremorine concentration could be linked to the progressive increase in the excitation state of spinal networks and recruitment of spinal neurons [ 34 , 35 ].…”

Section: Resultsmentioning

confidence: 99%

Cholinergic-mediated coordination of rhythmic sympathetic and motor activities in the newborn rat spinal cord

2018

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Here, we investigated intrinsic spinal cord mechanisms underlying the physiological requirement for autonomic and somatic motor system coupling. Using an in vitro spinal cord preparation from newborn rat, we demonstrate that the specific activation of muscarinic cholinergic receptors (mAchRs) (with oxotremorine) triggers a slow burst rhythm in thoracic spinal segments, thereby revealing a rhythmogenic capability in this cord region. Whereas axial motoneurons (MNs) were rhythmically activated during both locomotor activity and oxotremorine-induced bursting, intermediolateral sympathetic preganglionic neurons (IML SPNs) exhibited rhythmicity solely in the presence of oxotremorine. This somato-sympathetic synaptic drive shared by MNs and IML SPNs could both merge with and modulate the locomotor synaptic drive produced by the lumbar motor networks. This study thus sheds new light on the coupling between somatic and sympathetic systems and suggests that an intraspinal network that may be conditionally activated under propriospinal cholinergic control constitutes at least part of the synchronizing mechanism.

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“…That would provide an allocentric explanation for the central proprioceptive disturbances, which are often posited as the actual pathogenesis of PD ( Abbruzzese and Berardelli, 2003 ; Contreras-Vidal and Gold, 2004 ; Jacobs and Horak, 2006 ; Fiorio et al, 2007 ; Rand et al, 2010 ; Lee et al, 2013 ). In addition there is also peripheral fusimotor activity of the muscle spindle ( Radovanovic et al, 2015 ), the afferent spinal dorsal horn ( Skoog and Noga, 1995 ; Garraway and Hochman, 2001 ; Milla-Cruz et al, 2020 ), and its efferent paths along the ventral horn ( Yoshida and Tanaka, 1988 ; Weil-Fugazza and Godefroy, 1993 ; Barriere et al, 2004 ; Han et al, 2007 ; Zhu et al, 2007 ; Schwarz and Peever, 2011 ; Clemens et al, 2012 ; Sharples, 2017 ; Rivera-Oliver et al, 2019 ), all of which are disturbed in DD. This apparatus is controlled by the CNS ( Ellaway et al, 2015 ; Macefield and Knellwolf, 2018 ), with fusimotor activity operating as a “forward sensory model” ( Dimitriou and Edin, 2010 ).…”

Section: Hypotheses: Dopamine-depleted Grid Cells Evoke Parkinson’s S...mentioning

confidence: 99%

Grid cells: the missing link in understanding Parkinson’s disease?

Reinshagen

2024

Front. Neurosci.

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The mechanisms underlying Parkinson’s disease (PD) are complex and not fully understood, and the box-and-arrow model among other current models present significant challenges. This paper explores the potential role of the allocentric brain and especially its grid cells in several PD motor symptoms, including bradykinesia, kinesia paradoxa, freezing of gait, the bottleneck phenomenon, and their dependency on cueing. It is argued that central hubs, like the locus coeruleus and the pedunculopontine nucleus, often narrowly interpreted in the context of PD, play an equally important role in governing the allocentric brain as the basal ganglia. Consequently, the motor and secondary motor (e.g., spatially related) symptoms of PD linked with dopamine depletion may be more closely tied to erroneous computation by grid cells than to the basal ganglia alone. Because grid cells and their associated central hubs introduce both spatial and temporal information to the brain influencing velocity perception they may cause bradykinesia or hyperkinesia as well. In summary, PD motor symptoms may primarily be an allocentric disturbance resulting from virtual faulty computation by grid cells revealed by dopamine depletion in PD.

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Dopamine Pumping Up Spinal Locomotor Network Function

Cited by 4 publications

References 30 publications

Integration of Descending Command Systems for the Generation of Context-Specific Locomotor Behaviors

Integration of Descending Command Systems for the Generation of Context-Specific Locomotor Behaviors

Cholinergic-mediated coordination of rhythmic sympathetic and motor activities in the newborn rat spinal cord

Grid cells: the missing link in understanding Parkinson’s disease?

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