Modulation of Dorsal Spinocerebellar Responses to Limb Movement. I. Effect of Serotonin

Bosco, Gianfranco; Rankin, A.; Poppele, R. E.

doi:10.1152/jn.00203.2003

Cited by 13 publications

(6 citation statements)

References 32 publications

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“…This putative sensory modulation role is consistent with the presence of 5-HT receptors in the dorsal horn of the lumbosacral spinal cord (Liu et al, 2002). Furthermore, numerous findings associate 5-HT with sensory input modulation (Machacek et al, 2001;Meuser et al, 2002;Miquel et al, 2002;Shay and Hochman, 2002;Bosco et al, 2003;Hains et al, 2003). In intact cats, monoamine release selectively increases the excitability of some reflex circuits but decreases the excitability of others, e.g., potentiating transmission from group I spindle fibers and tendon organs (Edgley et al, 1988;Bras et al, 1990) while depressing transmission from nociceptors and group II fibers (Headley et al, 1978; Figure 5.…”

Section: Discussionsupporting

confidence: 78%

Spinal Cord-Transected Mice Learn to Step in Response to Quipazine Treatment and Robotic Training

Fong¹,

Cai²,

Otoshi³

et al. 2005

J. Neurosci.

131

126

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In the present study, concurrent treatment with robotic step training and a serotonin agonist, quipazine, generated significant recovery of locomotor function in complete spinal cord-transected mice (T7-T9) that otherwise could not step. The extent of recovery achieved when these treatments were combined exceeded that obtained when either treatment was applied independently. We quantitatively analyzed the stepping characteristics of spinal mice after alternatively administering no training, manual training, robotic training, quipazine treatment, or a combination of robotic training with quipazine treatment, to examine the mechanisms by which training and quipazine treatment promote functional recovery. Using fast Fourier transform and principal components analysis, significant improvements in the step rhythm, step shape consistency, and number of weight-bearing steps were observed in robotically trained compared with manually trained or nontrained mice. In contrast, manual training had no effect on stepping performance, yielding no improvement compared with nontrained mice. Daily bolus quipazine treatment acutely improved the step shape consistency and number of steps executed by both robotically trained and nontrained mice, but these improvements did not persist after quipazine was withdrawn. At the dosage used (0.5 mg/kg body weight), quipazine appeared to facilitate, rather than directly generate, stepping, by enabling the spinal cord neural circuitry to process specific patterns of sensory information associated with weight-bearing stepping. Via this mechanism, quipazine treatment enhanced kinematically appropriate robotic training. When administered intermittently during an extended period of robotic training, quipazine revealed training-induced stepping improvements that were masked in the absence of the pharmacological treatment.

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Section: Discussionsupporting

confidence: 78%

Spinal Cord-Transected Mice Learn to Step in Response to Quipazine Treatment and Robotic Training

Fong¹,

Cai²,

Otoshi³

et al. 2005

J. Neurosci.

131

126

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show abstract

“…At present, however, support for our assumptions from in vivo recordings seems relatively strong. All recordings of MFs in awake animals during natural behavior seem to support the interpretation that MFs operate with rate coding, in particular for the spinocerebellar systems and within the limb control zones that we are considering here [46], [49]–[52], [85], [86] but also for MFs in the oculomotor controlling regions of the cerebellum [48] and quite possibly also for vestibulocerebellum [47]. Also Golgi cells seem to follow the rate coding principle in relation to controlled movement [48], [47].…”

Section: Discussionsupporting

confidence: 73%

Processing of Multi-dimensional Sensorimotor Information in the Spinal and Cerebellar Neuronal Circuitry: A New Hypothesis

Spanne

Jörntell

2013

PLoS Comput Biol

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Why are sensory signals and motor command signals combined in the neurons of origin of the spinocerebellar pathways and why are the granule cells that receive this input thresholded with respect to their spike output? In this paper, we synthesize a number of findings into a new hypothesis for how the spinocerebellar systems and the cerebellar cortex can interact to support coordination of our multi-segmented limbs and bodies. A central idea is that recombination of the signals available to the spinocerebellar neurons can be used to approximate a wide array of functions including the spatial and temporal dependencies between limb segments, i.e. information that is necessary in order to achieve coordination. We find that random recombination of sensory and motor signals is not a good strategy since, surprisingly, the number of granule cells severely limits the number of recombinations that can be represented within the cerebellum. Instead, we propose that the spinal circuitry provides useful recombinations, which can be described as linear projections through aspects of the multi-dimensional sensorimotor input space. Granule cells, potentially with the aid of differentiated thresholding from Golgi cells, enhance the utility of these projections by allowing the Purkinje cell to establish piecewise-linear approximations of non-linear functions. Our hypothesis provides a novel view on the function of the spinal circuitry and cerebellar granule layer, illustrating how the coordinating functions of the cerebellum can be crucially supported by the recombinations performed by the neurons of the spinocerebellar systems.

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“…Consistent with this, both 5HT and NE facilitate the group I input to ventral spinocerebellar cells 55. Also, the impact of monoamines on the dorsal spinocerebellar system appears to be one of increasing one type of sensory information (limb axis orientation) compared to others 27. Finally, recent results in motoneurons,84, 99 considered in more detail below, indicate that the monoamines act to increase the sensitivity of the motoneuron to both excitation and inhibition.…”

Section: Overview Of Neuromodulatory Input To the Spinal Cordmentioning

confidence: 53%

Persistent inward currents in motoneuron dendrites: Implications for motor output

Heckman¹,

Gorassini²,

Bennett³

2004

Muscle and Nerve

380

341

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The dendrites of motoneurons are not, as once thought, passive conduits for synaptic inputs. Instead they have voltage-dependent channels that provide the capacity to generate a very strong persistent inward current (PIC). The amplitude of the PIC is proportional to the level of neuromodulatory input from the brainstem, which is mediated primarily by the monoamines serotonin and norepinephrine. During normal motor behavior, monoaminergic drive is likely to be moderately strong and the dendritic PIC generates many of the characteristic features of motor unit firing patterns. Most of the PIC activates at or below recruitment threshold and thus motor unit firing patterns exhibit a linear increase just above recruitment. The dendritic PIC allows motor unit derecruitment to occur at a lower input level than recruitment, thus providing sustained tonic firing with little or no synaptic input, especially in low-threshold units. However the dendritic PIC can be readily deactivated by synaptic inhibition. The overall amplification due to the dendritic PIC and other effects of monoamines on motoneurons greatly increases the input-output gain of the motor pool. Thus the brainstem neuromodulatory input provides a mechanism by which the excitability of motoneurons can be varied for different motor behaviors. This control system is lost in spinal cord injury but PICs nonetheless recover near-normal amplitudes in the months following the initial injury. The relationship of these findings to the cause of the spasticity syndrome developing after spinal cord injury is discussed.

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Modulation of Dorsal Spinocerebellar Responses to Limb Movement. I. Effect of Serotonin

Cited by 13 publications

References 32 publications

Spinal Cord-Transected Mice Learn to Step in Response to Quipazine Treatment and Robotic Training

Spinal Cord-Transected Mice Learn to Step in Response to Quipazine Treatment and Robotic Training

Processing of Multi-dimensional Sensorimotor Information in the Spinal and Cerebellar Neuronal Circuitry: A New Hypothesis

Persistent inward currents in motoneuron dendrites: Implications for motor output

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