Sensory-evoked perturbations of locomotor activity by sparse sensory input: a computational study

Sensory inputs from muscle, cutaneous, and joint afferents project to the spinal cord, where they are able to affect ongoing locomotor activity. Activation of sensory input can initiate or prolong bouts of locomotor activity depending on the identity of the sensory afferent activated and the timing of the activation within the locomotor cycle. However, the mechanisms by which afferent activity modifies locomotor rhythm and the distribution of sensory afferents to the spinal locomotor networks have not been determined. Considering the many sources of sensory inputs to the spinal cord, determining this distribution would provide insights into how sensory inputs are integrated to adjust ongoing locomotor activity. We asked whether a sparsely distributed set of sensory inputs could modify ongoing locomotor activity. To address this question, several computational models of locomotor central pattern generators (CPGs) that were mechanistically diverse and generated locomotor-like rhythmic activity were developed. We show that sensory inputs restricted to a small subset of the network neurons can perturb locomotor activity in the same manner as seen experimentally. Furthermore, we show that an architecture with sparse sensory input improves the capacity to gate sensory information by selectively modulating sensory channels. These data demonstrate that sensory input to rhythm-generating networks need not be extensively distributed.

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Patrick David Wall. 5 April 1925—8 August 2001

Biographical Memoirs of Fellows of the Royal Society ◽

10.1098/rsbm.2021.0014 ◽

2021 ◽

Author(s):

Maria Fitzgerald

Keyword(s):

Spinal Cord ◽

Dorsal Horn ◽

Sensory Input ◽

Molecular Genetic ◽

Sensory Information ◽

Spinal Cord Dorsal Horn ◽

Genetic Dissection ◽

Sensory Inputs ◽

Gate Control Theory ◽

The Usa

Patrick (Pat) Wall was a neurophysiologist and true pioneer in the science of pain. He discovered that the sensory information arising from receptors in our body, such as those for touch and heat, could be modified, or ‘gated’, in the spinal cord by other sensory inputs and also by information descending from the brain; this meant, as is now well recognized, that the final sensory experience is not necessarily predictable from the original pain-eliciting sensory input. He used this to explain the poor relationship between injury and pain, and to illustrate the fallacy of judging what someone ‘should’ be feeling from the sensory input alone. In 1969, together with his colleague, Ron Melzack, Pat proposed the ‘gate control theory of pain’ and the circuit diagram that summarized how central spinal cord circuits can modulate sensory inputs. Later on, he began to regret that ‘goddamned diagram’, which had come to dominate his life and work, but, like all great models, it paved the way for the future. Now, over 50 years after it was first published, molecular genetic dissection of dorsal horn neuronal circuitry has indisputably confirmed that sensory inputs are indeed ‘gated’ in the spinal cord dorsal horn. Through a career that started with a medical degree in Oxford, followed by almost 20 years at Yale and MIT in the USA, and continued at University College London, Pat Wall was a highly influential, critical, creative and original thinker who revolutionized our understanding of the relationship between injury and pain, and who also became a champion for all who suffered from chronic pain.

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Effects of Noradrenaline on Locomotor Rhythm–Generating Networks in the Isolated Neonatal Rat Spinal Cord

Journal of Neurophysiology ◽

10.1152/jn.1999.82.2.741 ◽

1999 ◽

Vol 82 (2) ◽

pp. 741-746 ◽

Cited By ~ 69

Author(s):

Ole Kiehn ◽

Keith T. Sillar ◽

Ole Kjaerulff ◽

Jonathan R. McDearmid

Keyword(s):

Spinal Cord ◽

Locomotor Activity ◽

Motor Activity ◽

Ventral Root ◽

Time Dependent ◽

Neonatal Rat ◽

Root Activity ◽

Rat Spinal Cord ◽

Locomotor Rhythm ◽

Variable Nature

We have studied the effects of the biogenic amine noradrenaline (NA) on motor activity in the isolated neonatal rat spinal cord. The motor output was recorded with suction electrodes from the lumbar ventral roots. When applied on its own, NA (0.5–50 μM) elicited either no measurable root activity, or activity of a highly variable nature. When present, the NA-induced activity consisted of either low levels of unpatterned tonic discharges, or an often irregular, slow rhythm that displayed a high degree of synchrony between antagonistic motor pools. Finally, in a few cases, NA induced a slow locomotor-like rhythm, in which activity alternated between the left and right sides, and between rostral and caudal roots on the same side. As shown previously, stable locomotor activity could be induced by bath application of N-methyl-d-aspartate (NMDA; 4–8.5 μM) and/or serotonin (5-HT; 4–20 μM). NA modulated this activity by decreasing the cycle frequency and increasing the ventral root burst duration. These effects were dose dependent in the concentration range 1–5 μM. In contrast, at no concentration tested did NA have consistent effects on burst amplitudes or on the background activity of the ongoing rhythm. Moreover, NA did not obviously affect the left/right and rostrocaudal alternation of the NMDA/5-HT rhythm. The NMDA/5-HT locomotor rhythm sometimes displayed a time-dependent breakdown in coordination, ultimately resulting in tonic ventral root activity. However, the addition of NA to the NMDA/5-HT saline could reinstate a well-coordinated locomotor rhythm. We conclude that exogenously applied NA can elicit tonic activity or can trigger a slow, irregular and often synchronous motor pattern. When NA is applied during ongoing locomotor activity, the amine has a distinct slowing effect on the rhythm while preserving the normal coordination between flexors and extensors. The ability of NA to “rescue” rhythmic locomotor activity after its time-dependent deterioration suggests that the amine may be important in the maintenance of rhythmic motor activity.

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Recent Insights into the Rhythmogenic Core of the Locomotor CPG

International Journal of Molecular Sciences ◽

10.3390/ijms22031394 ◽

2021 ◽

Vol 22 (3) ◽

pp. 1394

Author(s):

Vladimir Rancic ◽

Simon Gosgnach

Keyword(s):

Neural Network ◽

Spinal Cord ◽

Muscle Activation ◽

Central Pattern Generators ◽

Cell Types ◽

Genetic Approach ◽

Spinal Neurons ◽

Locomotor Rhythm ◽

Key Features ◽

Pattern Generators

In order for locomotion to occur, a complex pattern of muscle activation is required. For more than a century, it has been known that the timing and pattern of stepping movements in mammals are generated by neural networks known as central pattern generators (CPGs), which comprise multiple interneuron cell types located entirely within the spinal cord. A genetic approach has recently been successful in identifying several populations of spinal neurons that make up this neural network, as well as the specific role they play during stepping. In spite of this progress, the identity of the neurons responsible for generating the locomotor rhythm and the manner in which they are interconnected have yet to be deciphered. In this review, we summarize key features considered to be expressed by locomotor rhythm-generating neurons and describe the different genetically defined classes of interneurons which have been proposed to be involved.

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Active Role of Self-Sustained Neural Activity on Sensory Input Processing: A Minimal Theoretical Model

Neural Computation ◽

10.1162/neco_a_01471 ◽

2022 ◽

pp. 1-30

Author(s):

Bruno A. Santos ◽

Rogerio M. Gomes ◽

Xabier E. Barandiaran ◽

Phil Husbands

Keyword(s):

Neural Activity ◽

Sensory Input ◽

Categorical Perception ◽

Active Role ◽

Cross Product ◽

Dynamical Analysis ◽

Oscillatory Activity ◽

Sensory Inputs ◽

Input Processing ◽

Sensory Evoked

Abstract A growing body of work has demonstrated the importance of ongoing oscillatory neural activity in sensory processing and the generation of sensorimotor behaviors. It has been shown, for several different brain areas, that sensory-evoked neural oscillations are generated from the modulation by sensory inputs of inherent self-sustained neural activity (SSA). This letter contributes to that strand of research by introducing a methodology to investigate how much of the sensory-evoked oscillatory activity is generated by SSA and how much is generated by sensory inputs within the context of sensorimotor behavior in a computational model. We develop an abstract model consisting of a network of three Kuramoto oscillators controlling the behavior of a simulated agent performing a categorical perception task. The effects of sensory inputs and SSAs on sensory-evoked oscillations are quantified by the cross product of velocity vectors in the phase space of the network under different conditions (disconnected without input, connected without input, and connected with input). We found that while the agent is carrying out the task, sensory-evoked activity is predominantly generated by SSA (93.10%) with much less influence from sensory inputs (6.90%). Furthermore, the influence of sensory inputs can be reduced by 10.4% (from 6.90% to 6.18%) with a decay in the agent's performance of only 2%. A dynamical analysis shows how sensory-evoked oscillations are generated from a dynamic coupling between the level of sensitivity of the network and the intensity of the input signals. This work may suggest interesting directions for neurophysiological experiments investigating how self-sustained neural activity influences sensory input processing, and ultimately affects behavior.

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Mechanosensory inputs to the central pattern generators for locomotion in the lamprey spinal cord: resetting, entrainment, and computer modeling

Journal of Neurophysiology ◽

10.1152/jn.1993.70.6.2442 ◽

1993 ◽

Vol 70 (6) ◽

pp. 2442-2454 ◽

Cited By ~ 33

Author(s):

A. D. McClellan ◽

W. Jang

Keyword(s):

Spinal Cord ◽

Cycle Time ◽

Central Pattern Generators ◽

Phase Delay ◽

Phase Advance ◽

Response Curves ◽

Locomotor Rhythm ◽

Cycle Times ◽

Pattern Generators

1. Mechanoreceptors in the lamprey spinal cord have inputs to the central pattern generator (CPG) for locomotion. In the present study, imposed sinusoidal and pulsed movements were applied to the end of the in vitro lamprey spinal cord to excite the mechanoreceptors so that the relationship between entrainment and resetting of the locomotor rhythm could be examined. 2. The range over which the locomotor rhythm could be entrained by sinusoidal movements was asymmetric and occurred mostly at movement cycle times below the resting cycle time. During entrainment at the shortest cycle times, the movement phases were relatively small. 3. The phase response curves (PRCs) displayed the greatest shortening of cycle times (phase advance) for movement pulses applied during the first half of the locomotor cycle, whereas movement pulses applied during the second half of the cycle were largely ineffective. The amplitude of phase shifts in the PRC correlated with the ranges of cycle times over which entrainment occurred. 4. During resetting from movement pulses applied early in the cycle, the burst and interburst parts of the cycle shortened by about the same percentage. In addition, resetting effects occurred simultaneously along the spinal cord, suggesting a rapid distribution of timing information. 5. A computer model of the CPGs, consisting of left and right oscillators and inputs from mechanosensory elements, produced entrainment ranges that were symmetric around the resting cycle time. The PRCs from the model showed phase advance for movement pulses applied during the first half of the cycle and phase delay for pulses applied during the second half of the cycle. 6. Because of the asymmetric experimental PRCs for the lamprey spinal cord, gating was incorporated into the cooffter model such that oscillators on one side of the model gated inputs from mechanosensory elements on the same side. With gating, the model produced entrainment ranges that were asymmetric and confined to cycle times below the resting cycle time. The PRCs still showed phase advance for pulses applied at the beginning of the cycle, and the amount of phase delay produced during the second half of the cycle was substantially reduced compared with the simulations without gating.

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Thoracoabdominalis aortakirekesztés során fellépő elektrofiziológiai változások a gerincvelőben

Magyar Sebészet (Hungarian Journal of Surgery) ◽

10.1556/1046.73.2020.4.5 ◽

2020 ◽

Vol 73 (4) ◽

pp. 160-166

Author(s):

Csaba Dzsinich ◽

Péter Gloviczki ◽

Gabriella Nagy ◽

Klaudia Vivien Nagy

Keyword(s):

Spinal Cord ◽

Motor Evoked Potentials ◽

Spinal Cord Ischemia ◽

Experimental Studies ◽

Neuron Specific Enolase ◽

Neurological Complications ◽

Neurologic Outcome ◽

Published Data ◽

Aortic Clamping ◽

Sensory Evoked

Összefoglaló. A thoracoabdominalis aortakirekesztés okozta gerincvelő ischemia súlyos neurológiai következményeit számos klinikai és kísérleti tanulmány bizonyítja. E nehezen kiszámítható, súlyos szövődmény megelőzésének érdekében régi törekvés megfelelő intra- és posztoperatív monitorizálás kifejlesztése, ami előre jelzi a gerincvelő-funkció romlását, illetve a kialakuló celluláris károsodást. A legelterjedtebb, a klinikai gyakorlatban széles körben alkalmazott megoldás a gerincvelői kiváltott motoros potenciál (MEP) folyamatos ellenőrzése. Ritkábban alkalmazott – bár ígéretes – eljárás a biokémiai változások nyomon követése, ami a sejtszintű károsodás markereit használja fel az ischemia okozta változások felismerésére. Korábbi dolgozatunkban kutyákon végzett kísérleteink azon eredményeit ismertettük, amelyekben a 60 perces thoracoabdominalis aortakirekesztés okozta neurológiai változások és a perfúzió adatainak összefüggéseit tárgyaltuk. Jelen tanulmányunkban a gerincvelői motoros (MEP) és szenzoros (SEP) kiváltott potenciálok változásait vizsgáljuk a neurológiai végállapot vonatkozásában. Megállapítottuk, hogy SEP változásai a neurológiai károsodás mértékével értékelhető összefüggést nem mutatnak. A MEP-amplitúdó és -latencia értékei biztonsággal jelzik a fenyegető gerincvelő ischemiát. A neurológiai deficit mélységét (Tarlov 2,1,0) a MEP-értékek változásai numerikusan nem értékelhetően követik. Summary. Severe neurological complications of the thoracoabdominal aortic clamping were published in numerous clinical and experimental studies. These hardly predictable, devastating consequences demanded to develop a monitoring system which might detect impending level of spinal cord ischemia in time – in order to introduce or enhance protective procedures and prevent permanent neurological deficit. The most widely used monitoring in clinical practice is the continuous surveillance of the motor evoked potentials (MEP) during and after thoracoabdominal aortic clamping. Much less used, but promising opportunity is to control the metabolic changes and cellular integrity utilizing specific markers like liquor lactate and neuron specific enolase (NSE) etc. In our earlier study we published data of our canine experiment related to coherencies between neurological outcome and specific perfusion of the spinal cord during and after one hour thoracoabdominal aortic clamping. In the present paper we investigate the behavior of motor evoked (MEP) and sensory evoked (SEP) potentials related to neurological changes. We conclude the behavior of SEP values hardly correlate with the neurologic outcome, meanwhile decrease of MEP amplitude provides reliable signal for developing spinal cord ischemia. We could not confirm a numeric correlation of these data and the level of the final neurologic outcome.

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A combined experimental and computational study of mechanical properties after balloon kyphoplasty

Proceedings of the Institution of Mechanical Engineers Part H Journal of Engineering in Medicine ◽

10.1177/09544119211013927 ◽

2021 ◽

pp. 095441192110139

Author(s):

Philip Purcell ◽

Fiona McEvoy ◽

Stephen Tiernan ◽

Derek Sweeney ◽

Seamus Morris

Keyword(s):

Computational Models ◽

Computational Study ◽

Case Reports ◽

Experimental Tests ◽

Balloon Kyphoplasty ◽

Fatigue Tests ◽

Vertebral Compression Fractures ◽

Baseline Case ◽

Strength And Stiffness ◽

Stiffness Loss

Vertebral compression fractures rank among the most frequent injuries to the musculoskeletal system, with more than 1 million fractures per annum worldwide. The past decade has seen a considerable increase in the utilisation of surgical procedures such as balloon kyphoplasty to treat these injuries. While many kyphoplasty studies have examined the risk of damage to adjacent vertebra after treatment, recent case reports have also emerged to indicate the potential for the treated vertebra itself to re-collapse after surgery. The following study presents a combined experimental and computational study of balloon kyphoplasty which aims to establish a methodology capable of evaluating these cases of vertebral re-collapse. Results from both the experimental tests and computational models showed significant increases in strength and stiffness after treatment, by factors ranging from 1.44 to 1.93, respectively. Fatigue tests on treated specimens showed a 37% drop in the rate of stiffness loss compared to the untreated baseline case. Further analysis of the computational models concluded that inhibited PMMA interdigitation at the interface during kyphoplasty could reverse improvements in strength and stiffness that could otherwise be gained by the treatment.

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Rostrocaudal Distribution of the C-Fos-Immunopositive Spinal Network Defined by Muscle Activity during Locomotion

Brain Sciences ◽

10.3390/brainsci11010069 ◽

2021 ◽

Vol 11 (1) ◽

pp. 69

Author(s):

Natalia Merkulyeva ◽

Vsevolod Lyakhovetskii ◽

Aleksandr Veshchitskii ◽

Oleg Gorskii ◽

Pavel Musienko

Keyword(s):

Spinal Cord ◽

Locomotor Activity ◽

Control Systems ◽

Muscle Activity ◽

Knee Extensors ◽

Emg Activity ◽

Lumbosacral Spinal Cord ◽

Adductor Muscles ◽

Spinal Network ◽

Hip Flexor

The optimization of multisystem neurorehabilitation protocols including electrical spinal cord stimulation and multi-directional tasks training require understanding of underlying circuits mechanisms and distribution of the neuronal network over the spinal cord. In this study we compared the locomotor activity during forward and backward stepping in eighteen adult decerebrated cats. Interneuronal spinal networks responsible for forward and backward stepping were visualized using the C-Fos technique. A bi-modal rostrocaudal distribution of C-Fos-immunopositive neurons over the lumbosacral spinal cord (peaks in the L4/L5 and L6/S1 segments) was revealed. These patterns were compared with motoneuronal pools using Vanderhorst and Holstege scheme; the location of the first peak was correspondent to the motoneurons of the hip flexors and knee extensors, an inter-peak drop was presumably attributed to the motoneurons controlling the adductor muscles. Both were better expressed in cats stepping forward and in parallel, electromyographic (EMG) activity of the hip flexor and knee extensors was higher, while EMG activity of the adductor was lower, during this locomotor mode. On the basis of the present data, which showed greater activity of the adductor muscles and the attributed interneuronal spinal network during backward stepping and according with data about greater demands on postural control systems during backward locomotion, we suppose that the locomotor networks for movements in opposite directions are at least partially different.

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Descending propriospinal neurons mediate restoration of locomotor function following spinal cord injury

Journal of Neurophysiology ◽

10.1152/jn.00544.2016 ◽

2017 ◽

Vol 117 (1) ◽

pp. 215-229 ◽

Cited By ~ 10

Author(s):

Katelyn N. Benthall ◽

Ryan A. Hough ◽

Andrew D. McClellan

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Axonal Regeneration ◽

Central Pattern Generators ◽

Burst Activity ◽

Compensatory Mechanism ◽

Spinal Lesions ◽

Cord Injury ◽

Recovery Times ◽

Indirect Activation

Following spinal cord injury (SCI) in the lamprey, there is virtually complete recovery of locomotion within a few weeks, but interestingly, axonal regeneration of reticulospinal (RS) neurons is mostly limited to short distances caudal to the injury site. To explain this situation, we hypothesize that descending propriospinal (PS) neurons relay descending drive from RS neurons to indirectly activate spinal central pattern generators (CPGs). In the present study, the contributions of PS neurons to locomotor recovery were tested in the lamprey following SCI. First, long RS neuron projections were interrupted by staggered spinal hemitransections on the right side at 10% body length (BL; normalized from the tip of the oral hood) and on the left side at 30% BL. For acute recovery conditions (≤1 wk) and before axonal regeneration, swimming muscle burst activity was relatively normal, but with some deficits in coordination. Second, lampreys received two spaced complete spinal transections, one at 10% BL and one at 30% BL, to interrupt long-axon RS neuron projections. At short recovery times (3–5 wk), RS and PS neurons will have regenerated their axons for short distances and potentially established a polysynaptic descending command pathway. At these short recovery times, swimming muscle burst activity had only minor coordination deficits. A computer model that incorporated either of the two spinal lesions could mimic many aspects of the experimental data. In conclusion, descending PS neurons are a viable mechanism for indirect activation of spinal locomotor CPGs, although there can be coordination deficits of locomotor activity. NEW & NOTEWORTHY In the lamprey following spinal lesion-mediated interruption of long axonal projections of reticulospinal (RS) neurons, sensory stimulation still elicited relatively normal locomotor muscle burst activity, but with some coordination deficits. Computer models incorporating the spinal lesions could mimic many aspects of the experimental results. Thus, after disruption of long-axon projections from RS neurons in the lamprey, descending propriospinal (PS) neurons appear to be a viable compensatory mechanism for indirect activation of spinal locomotor networks.

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