Pharmacology of neural mechanisms of the motor system with reference to the spinal cord.

Despite substantial advances in the field, particularly resulting from physiological studies in animals, the neural mechanisms underlying the generation of many motor behaviors in humans remain unclear. A recent study (Cappellini G et al. J Neurophysiol 104: 3064–3073, 2010) sheds more light on this topic. Like the string of a violin, the α-motoneuron pools in the spinal cord during locomotion show continuous and oscillatory patterns of activation. In this report, the implications and relevance of this finding are discussed in a general framework that includes neurophysiology, optimal control theory, and robotics.

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Evolution of the vertebrate motor system — from forebrain to spinal cord

Current Opinion in Neurobiology ◽

10.1016/j.conb.2021.07.016 ◽

2021 ◽

Vol 71 ◽

pp. 11-18

Author(s):

Sten Grillner

Keyword(s):

Spinal Cord ◽

Motor System

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Spinal microcircuits comprising dI3 interneurons are necessary for motor functional recovery following spinal cord transection

eLife ◽

10.7554/elife.21715 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 20

Author(s):

Tuan V Bui ◽

Nicolas Stifani ◽

Turgay Akay ◽

Robert M Brownstone

Keyword(s):

Spinal Cord ◽

Functional Recovery ◽

Motor System ◽

Motor Training ◽

Prediction Errors ◽

Spinal Interneurons ◽

Motor Activities ◽

Afferent Inputs ◽

To Receive ◽

Sensory Prediction

The spinal cord has the capacity to coordinate motor activities such as locomotion. Following spinal transection, functional activity can be regained, to a degree, following motor training. To identify microcircuits involved in this recovery, we studied a population of mouse spinal interneurons known to receive direct afferent inputs and project to intermediate and ventral regions of the spinal cord. We demonstrate that while dI3 interneurons are not necessary for normal locomotor activity, locomotor circuits rhythmically inhibit them and dI3 interneurons can activate these circuits. Removing dI3 interneurons from spinal microcircuits by eliminating their synaptic transmission left locomotion more or less unchanged, but abolished functional recovery, indicating that dI3 interneurons are a necessary cellular substrate for motor system plasticity following transection. We suggest that dI3 interneurons compare inputs from locomotor circuits with sensory afferent inputs to compute sensory prediction errors that then modify locomotor circuits to effect motor recovery.

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Multiple Effects of Serotonin and Acetylcholine on Hyperpolarization-Activated Inward Current in Locomotor Activity-Related Neurons in Cfos-EGFP Mice

Journal of Neurophysiology ◽

10.1152/jn.01110.2009 ◽

2010 ◽

Vol 104 (1) ◽

pp. 366-381 ◽

Cited By ~ 13

Author(s):

Yue Dai ◽

Larry M. Jordan

Keyword(s):

Spinal Cord ◽

Motor System ◽

Reversal Potential ◽

Rhythmic Activity ◽

Maximal Conductance ◽

Inward Current ◽

Spinal Interneurons ◽

Whole Cell Patch Clamp ◽

Activation Rate ◽

Maximal Activation

Hyperpolarization-activated inward current ( Ih) has been shown to be involved in production of bursting during various forms of rhythmic activity. However, details of Ih in spinal interneurons related to locomotion remain unknown. Using Cfos-EGFP transgenic mice (P6–P12) we are able to target the spinal interneurons activated by locomotion. Following a locomotor task, whole cell patch-clamp recordings were obtained from ventral EGFP+ neurons in spinal cord slices (T13–L4, 200–250 μm). Ih was found in 51% of EGFP+ neurons ( n = 149) with almost even distribution in lamina VII (51%), VIII (47%), and X (55%). Ih could be blocked by ZD7288 (10–20 μM) or cesium (1–1.5 mM) but was insensitive to barium (2–2.5 mM). Ih activated at −80.1 ± 9.2 mV with half-maximal activation −95.5 ± 13.3 mV, activation rate 10.0 ± 3.2 mV, time constant 745 ± 501 ms, maximal conductance 1.0 ± 0.7 nS, and reversal potential −34.3 ± 3.6 mV. 5-HT (15–20 μM) and ACh (20–30 μM) produced variable effects on Ih. 5-HT increased Ih in 43% of EGFP+ neurons ( n = 37), decreased Ih in 24%, and had no effect on Ih in 33% of the neurons. ACh decreased Ih in 67% of EGFP+ neurons ( n = 18) with unchanged Ih in 33% of the neurons. This study characterizes the Ih in locomotor-related interneurons and is the first to demonstrate the variable effects of 5-HT and ACh on Ih in rodent spinal interneurons. The finding of 5-HT and ACh-induced reduction of Ih in EGFP+ neurons suggests a novel mechanism that the motor system could use to limit the participation of certain neurons in locomotion.

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Pathophysiology of the lower urinary tract and CNS

Canadian Urological Association Journal ◽

10.5489/cuaj.708 ◽

2013 ◽

Vol 5 (5-S2) ◽

pp. 126

Author(s):

Christopher Chapple

Keyword(s):

Spinal Cord ◽

Central Nervous System ◽

Nervous System ◽

Urinary Tract ◽

Lower Urinary Tract ◽

Neural Control ◽

Neural Mechanisms ◽

The Other ◽

Bladder Function ◽

Lower Urinary

A number of aspects of neural control are potentially important inthe control of bladder function, including both sensory and motorand peripheral and central pathways. It is likely that a combinationof disorders of both central and peripheral neural mechanisms isimportant in the genesis of urgency and the other symptoms of theoveractive bladder (OAB). Given the number of potential pathwaysinvolved, potential pharmacologic targets for OAB exist in the CNS(central nervous system; cerebral cortex, midbrain, spinal cord)and periphery (LUT; lower urinary tract). Antimuscarinics are stillthe mainstay of OAB treatment, but there are also a number ofother potentially efficacious drugs that may also provide benefitagainst the neurologic components of OAB. This review discussesthe impact of neurological abnormalities on lower urinary tractsymptoms and the potential for treatments targeting these pathwaysto improve symptoms.

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Neural Mechanisms of Hyperalgesia: Peripheral or Central Sensitization?

Physiology ◽

10.1152/physiologyonline.1995.10.6.260 ◽

1995 ◽

Vol 10 (6) ◽

pp. 260-265

Author(s):

E Carstens

Keyword(s):

Spinal Cord ◽

Central Sensitization ◽

Pain Sensitivity ◽

Neural Mechanisms ◽

Neural Processes

Everyone has experienced soreness after an injury. What neural processes underlie this increased pain sensitivity (hyperalgesia)? Recent data indicate that injury triggers an increase in the sensitivity of spinal cord pain-signaling neurons. Nonpainful activation of these sensitized neurons evokes an exaggerated signal interpreted as pain.

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Neural mechanisms of intersegmental coordination in lamprey: local excitability changes modify the phase coupling along the spinal cord

Journal of Neurophysiology ◽

10.1152/jn.1992.67.2.373 ◽

1992 ◽

Vol 67 (2) ◽

pp. 373-388 ◽

Cited By ~ 99

Author(s):

T. Matsushima ◽

S. Grillner

Keyword(s):

Spinal Cord ◽

Forward Direction ◽

Neural Mechanisms ◽

Cycle Duration ◽

Phase Lag ◽

High Concentration ◽

Caudal Portion ◽

Bath Application ◽

Ventral Roots

1. To elucidate the neural mechanisms responsible for coordinating undulatory locomotor movements, the intersegmental phase lag was analyzed from ventral roots along the spinal cord during fictive swimming. It was induced by bath application of N-methyl-D-aspartate (NMDA) in in vitro preparations of lamprey spinal cord, while the excitability of different segments were modified. The phase lag between consecutive segments during normal forward swimming is 1% of the cycle duration in a broad range of values. Rostral segments are activated before more caudal ones. 2. Under control conditions, whole preparations (12-24 segment long; n = 22) were perfused with NMDA solutions of the same concentration (100-150 microM). The intersegmental phase lag values varied in a continuous range with a single peak around a median value of forward +0.74% per segment (range: forward +2.23% to backward -0.97%). 3. To examine whether excitability differences along the spinal cord could modify the intersegmental phase lag, different levels of excitatory amino acids (NMDA) were applied to spinal cord preparations positioned in a partitioned chamber. Different portions of the cord could be perfused separately by NMDA solutions of different concentrations (50-150 microM). If rostral segments were perfused with the higher NMDA solution, the lag was inevitably in the forward direction. Conversely, if the caudal portion was perfused with the higher NMDA solution, caudally located ventral roots became activated before the rostral ventral roots in a caudorostral succession, thus reversing the direction of the fictive swimming wave to propagate as during backward swimming. If the middle portion was perfused by the highest NMDA solution, this portion instead became leading, and the activity propagated from this point in both the rostral and the caudal directions. The portion located in the pool with highest NMDA concentration always gave rise to a "leading" segment. 4. When a portion of the preparation was perfused with an NMDA solution of a high concentration (75-150 microM), the cycle duration was close to that recorded when the whole preparation was perfused with the same high NMDA solution. The ensemble cycle duration is, therefore, largely determined by the leading segment. 5. The phase lag changes were not restricted to the region around the barrier separating pools with different NMDA solutions.(ABSTRACT TRUNCATED AT 400 WORDS)

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Rhythmic sympathetic nerve discharges in an in vitro neonatal rat brain stem-spinal cord preparation

Journal of Applied Physiology ◽

10.1152/jappl.1999.87.3.1066 ◽

1999 ◽

Vol 87 (3) ◽

pp. 1066-1074 ◽

Cited By ~ 17

Author(s):

Chun-Kuei Su

Keyword(s):

Spinal Cord ◽

Ascorbic Acid ◽

Brain Stem ◽

Sympathetic Nerve ◽

Power Spectral Analysis ◽

Neural Mechanisms ◽

Neonatal Rat ◽

Root Activity ◽

Superior Cerebellar Artery

To understand the origination of sympathetic nerve discharge (SND), I developed an in vitro brain stem-spinal cord preparation from neonatal rats. Ascorbic acid (3 mM) was added into the bath solution to increase the viability of preparations. At 24°C, rhythmic SND (recorded from the splanchnic nerve) was consistently observed, but it became quiescent at <16°C. Respiratory-related SND (rSND) was discernible and was well correlated with C4 root activity. Power spectral analysis of SND revealed a dominant 2-Hz oscillation. In most preparations (86%), such oscillation was persistent, whereas it only slightly reduced its magnitude after isolation from the brain stem. The removal of neural structures rostral to the superior cerebellar artery (equivalent to the level of facial nuclei) reduced rSND, increased tonic SND, but did not affect the temporal coupling between SND and C4 root activity. Our data suggest a prominent contribution of SND from the neural mechanisms confined within the neonatal rat spinal cord. This ascorbic acid-enhanced in vitro preparation is a very useful model to study neural mechanisms underlying sympathorespiratory integration.

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Cutaneous stimulation evokes long-lasting excitation of spinal interneurons in the turtle

Journal of Neurophysiology ◽

10.1152/jn.1990.64.4.1134 ◽

1990 ◽

Vol 64 (4) ◽

pp. 1134-1148 ◽

Cited By ~ 36

Author(s):

S. N. Currie ◽

P. S. Stein

Keyword(s):

Spinal Cord ◽

Receptive Field ◽

Action Potential ◽

Receptive Fields ◽

Neural Mechanisms ◽

Cutaneous Afferents ◽

Cutaneous Stimulation ◽

Single Action ◽

Single Action Potential ◽

Stimulation Of

1. We demonstrated multisecond increases in the excitability of the rostral-scratch reflex in the turtle by electrically stimulating the shell at sites within the rostral-scratch receptive field. To examine the cellular mechanisms for these multisecond increases in scratch excitability, we recorded from single cutaneous afferents and sensory interneurons that responded to stimulation of the shell within the rostral-scratch receptive field. A single segment of the midbody spinal cord (D4, the 4th postcervical segment) was isolated in situ by transecting the spinal cord at the segment's anterior and posterior borders. The isolated segment was left attached to its peripheral nerve that innervates part of the rostral-scratch receptive field. A microsuction electrode (4-5 microns ID) was used to record extracellularly from the descending axons of cutaneous afferents and interneurons in the spinal white matter at the posterior end of the D4 segment. 2. The turtle shell is innervated by slowly and rapidly adapting cutaneous afferents. All cutaneous afferents responded to a single electrical stimulus to the shell with a single action potential. Maintained mechanical stimulation applied to the receptive field of some slowly adapting afferents produced several seconds of afterdischarge at stimulus offset. We refer to the cutaneous afferent afterdischarge caused by mechanical stimulation of the shell as "peripheral afterdischarge." 3. Within the D4 spinal segment there were some interneurons that responded to a brief mechanical stimulus within their receptive fields on the shell with short afterdischarge and others that responded with long afterdischarge. Short-afterdischarge interneurons responded to a single electrical pulse to a site in their receptive fields either with a brief train of action potentials or with a single action potential. Long-afterdischarge interneurons responded to a single electrical shell stimulus with up to 30 s of afterdischarge. Long-afterdischarge interneurons also exhibited strong temporal summation in response to a pair of electrical shell stimuli delivered up to several seconds apart. Because all cutaneous afferents responded to an electrical shell stimulus with a single action potential, we conclude that electrically evoked afterdischarge in interneurons was produced by neural mechanisms in the spinal cord; we refer to this type of afterdischarge as "central afterdischarge." 4. These results demonstrate that neural mechanisms for long-lasting excitability changes in response to cutaneous stimulation reside in a single segment of the spinal cord. Cutaneous interneurons with long afterdischarge may serve as cellular loci for multise

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