Cord Central Pattern Generators Research Articles

Chapter 2 - Upper and lower motor neuron neurophysiology and motor control

This chapter considers the principles that underlie neurophysiological studies of upper motor neuron or lower motor neuron lesions, based on an understanding of the normal structure and function of the motor system. Human motor neurophysiology consists of an evaluation of the active components of the motor system that are relevant to volitional movements. Relatively primitive motor skills include locomotion, much dependent on the spinal cord central pattern generator, reaching, involving proximal and distal muscles activation, and grasping. Humans are well prepared to perform complex movements like writing. The role of motor cortex is critical for the motor activity, very dependent on the continuous sensory feedback, and this is essential for adapting the force and speed control, which contributes to motor learning. Most corticospinal neurons in the brain project to brainstem and spinal cord, many with polysynaptic inhibitory rather than excitatory connections. The monosynaptic connections observed in humans and primates constitute a specialized pathway implicated in fractional finger movements. Spinal cord has a complex physiology, and local reflexes and sensory feedback are essential to control adapted muscular contraction during movement. The cerebellum has a major role in motor coordination, but also consistent roles in sensory activities, speech, and language, in motor and spatial memory, and in psychological activity. The motor unit is the final effector of the motor drive. The complex interplay between the lower motor neuron, its axon, motor end-plates, and muscle fibers allows a relevant plasticity in the movement output.

Gait regulation using monopolar intraspinal micro-stimulation of spinal cord central pattern generator: New insights for improving Hodgkin–Huxley model

Restoring the motor function of paralyzed limbs has always been an important aim in the field of biomedical engineering. In view of the discovery of the repeatable experimental phenomenon that positive and negative stimulation pulses applied to specific points, identified as central pattern generator (CPG) sites, could induce switching of the movement patterns of bilateral hindlimbs, an improved Hodgkin–Huxley (HH) neuron model was established by introducing the electric field effect principle. A CPG neural network model comprising 12 neural units in six joints of the bilateral hindlimbs was modeled. The simulation results showed the alternating movement patterns of the bilateral hindlimbs through the action potential release of extensor and flexor neurons. The explosive electromyogram of the gastrocnemius (GM) and quadriceps femoris (QF) when stimulating the CPG sites with intraspinal micro-stimulation (ISMS) was consistent with the action potential diagram of the flexor and extensor neurons obtained via simulation. Our research considers the neural network model of electric field radiation, which can facilitate a deep understanding of the dynamic characteristics of neurons in the electric field environment, and verifies the correlation between the location of CPG sites, stimulus polarity and movement patterns to induce alternating left–right coordinated movements.

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

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.

Spinal neurons bursting in phase with fictive scratching are not related to spontaneous cord dorsum potentials

Spontaneous cord dorsum potentials (spontaneous CDPs) are produced by the activation of dorsal horn neurons distributed along the L4 to S1 spinal cord segments, in Rexed’s laminae III–VI, in the same region in which there are interneurons rhythmically bursting during fictive scratching in cats. An interesting observation is that spontaneous CDPs are not rhythmically superimposed on the sinusoidal CDPs generated during fictive scratching episodes, thus suggesting that the interneurons producing both types of CDPs belong to different spinal circuits. In order to provide experimental data to support this hypothesis, we recorded unitary activity of neurons in the L6 spinal cord segment. We found that the neurons firing rhythmically during the sinusoidal CDPs associated with the extensor, flexor or intermediate phases of scratching were not synchronized with the spontaneous CDPs. Moreover, we found that the neurons firing during the spontaneous CDPs were not synchronized with the sinusoidal CDPs. These results suggest that the neurons involved in the occurrence of spontaneous CDPs are not part of the spinal cord central pattern generators (CPGs). This study will be relevant for understanding the relationships between the spinal cord neuronal populations firing spontaneously and the CPGs, in the intact and injured spinal cord.

Dorsally derived spinal interneurons in locomotor circuits

During neuronal circuit formation, axons are guided to their targets by the help of axon guidance molecules, which are required for establishing functional circuits. A promising system to dissect the development and functionalities of neuronal circuitry is the spinal cord central pattern generator (CPG) for locomotion, which converts a tonic supraspinal drive to rhythmic and coordinated movements. Here we describe concepts arising from genetic studies of the locomotor network with a focus on the position and roles of commissural interneurons. In particular, this involves studies of several families of axon guidance molecules relevant for midline crossing, the Eph/ephrins and Netrin/DCC. Effects on developing commissural interneurons in mice with aberrant midline axon guidance capabilities suggest that, in addition to ventral populations, dorsal commissural interneurons also play a role in coordinating locomotor circuitry. Recent findings implicate the novel dI6 interneuron marker Dmrt3 in this role. Strikingly, mutations in Dmrt3 result in divergent gait patterns in both mice and horses.

Spinal Cord Electrophysiology II: Extracellular Suction Electrode Fabrication

Development of neural circuitries and locomotion can be studied using neonatal rodent spinal cord central pattern generator (CPG) behavior. We demonstrate a method to fabricate suction electrodes that are used to examine CPG activity, or fictive locomotion, in dissected rodent spinal cords. The rodent spinal cords are placed in artificial cerebrospinal fluid and the ventral roots are drawn into the suction electrode. The electrode is constructed by modifying a commercially available suction electrode. A heavier silver wire is used instead of the standard wire given by the commercially available electrode. The glass tip on the commercial electrode is replaced with a plastic tip for increased durability. We prepare hand drawn electrodes and electrodes made from specific sizes of tubing, allowing consistency and reproducibility. Data is collected using an amplifier and neurogram acquisition software. Recordings are performed on an air table within a Faraday cage to prevent mechanical and electrical interference, respectively.

Spinal Cord Electrophysiology II: Extracellular Suction Electrode Fabrication

Development of neural circuitries and locomotion can be studied using neonatal rodent spinal cord central pattern generator (CPG) behavior. We demonstrate a method to fabricate suction electrodes that are used to examine CPG activity, or fictive locomotion, in dissected rodent spinal cords. The rodent spinal cords are placed in artificial cerebrospinal fluid and the ventral roots are drawn into the suction electrode. The electrode is constructed by modifying a commercially available suction electrode. A heavier silver wire is used instead of the standard wire given by the commercially available electrode. The glass tip on the commercial electrode is replaced with a plastic tip for increased durability. We prepare hand drawn electrodes and electrodes made from specific sizes of tubing, allowing consistency and reproducibility. Data is collected using an amplifier and neurogram acquisition software. Recordings are performed on an air table within a Faraday cage to prevent mechanical and electrical interference, respectively.

EphA4-Dependent Axon Guidance Is Mediated by the RacGAP α2-Chimaerin

Neuronal network formation in the developing nervous system is dependent on the accurate navigation of nerve cell axons and dendrites, which is controlled by attractive and repulsive guidance cues. Ephrins and their cognate Eph receptors mediate many repulsive axonal guidance decisions by intercellular interactions resulting in growth cone collapse and axon retraction of the Eph-presenting neuron. We show that the Rac-specific GTPase-activating protein alpha2-chimaerin binds activated EphA4 and mediates EphA4-triggered axonal growth cone collapse. alpha-Chimaerin mutant mice display a phenotype similar to that of EphA4 mutant mice, including aberrant midline axon guidance and defective spinal cord central pattern generator activity. Our results reveal an alpha-chimaerin-dependent signaling pathway downstream of EphA4, which is essential for axon guidance decisions and neuronal circuit formation in vivo.

Belly dancer's myoclonus and chronic abdominal pain: Pain-related dysinhibition of a spinal cord central pattern generator?

We report on a patient with segmental rhythmic myoclonus resembling belly dance. This patient developed the myoclonus in temporal and anatomical association with chronic abdominal pain. No structural or metabolic abnormalities were found. EMG recordings suggested the presence of a spinal cord central pattern generator (CPG). We hypothesize that pain-related spinal plasticity might have contributed to the hyperactivity of a spinal CPG, thus leading to the myoclonic jerks in our patient.

Intraoperative Applications Of The H-Reflex And F-Response: A Tutorial

Traditional intraoperative monitoring of spinal cord function involves the use of three techniques: 1. Orthodromic ascending somatosensory evoked potentials (SSEPs) and 2. antIDromic descending neurogenic somatosensory evoked potentials (DNSSEPs) monitor long-tract sensory function. SSEPs and DNSSEPs do not monitor interneuronal gray matter function. 3. Transcranial motor evoked potentials (TMEPs) monitor descending long-tract motor function and measure interneuronal gray matter function by activating motor neurons. TMEPs activate from 4-5% of the motor neuron pool. When using TMEPs 95-96% of the motor spinal cord systems activating the motor neurons are not monitored. Our ability to interact with our environment involves not only intact sensation and strength, but also complex coordinated motor behavior. Complex coordinated motor behavior is controlled by groups of electrically-coupled spinal cord central pattern generators (CPGs). The components of CPGs are: descending and propriospinal systems, peripheral input, and segmental interneurons. The point-of-control is the level of excitation of interneurons, which is determined by the integrated activity of the other components. Spinal cord injury (SCI) changes segmental reflex gain by uncoupling these components. Changes in gain are detected by recordings from muscles. SSEPs, DNSSEPs and TMEPs provIDe limited information about the status of CPGs. H-reflexes measure the function of from 20-100% of the motor neuron pool. F-responses measure the function of from 1-5% of the motor neuron pool. H-reflexes and F-responses provIDe information about the degree of coupling between CPG components. Recording H-reflexes and F-responses together with SSEPs and TMEPs not only monitors spinal cord long-tract function, but also provIDes a multiple-systems approach that monitors those spinal cord systems that are responsible for the control of complex coordinated motor behavior. The objective of this paper is to describe how H-reflexes and F-responses can be used to monitor complex coordinated motor behavior.