Spinal CPG Research Articles

Emergence of Extreme Paw Accelerations During Cat Paw Shaking: Interactions of Spinal Central Pattern Generator, Hindlimb Mechanics and Muscle Length-Depended Feedback.

Cat paw shaking is a spinal reflex for removing an irritating stimulus from paw by developing extremely high paw accelerations. Previous studies of paw shaking revealed a proximal-to-distal gradient of hindlimb segmental velocities/accelerations, as well as complex inter-joint coordination: passive motion-dependent interaction moments acting on distal segments are opposed by distal muscle moments. However, mechanisms of developing extreme paw accelerations during paw shaking remain unknown. We hypothesized that paw-shaking mechanics and muscle activity might correspond to a whip-like mechanism of energy generation and transfer along the hindlimb. We first demonstrated in experiments with five intact, adult, female cats that during paw shaking, energy generated by proximal muscle moments was transmitted to distal segments by joint forces. This energy transfer was mostly responsible for the segmental velocity/acceleration proximal-to-distal gradient. Distal muscle moments mostly absorbed energy of the distal segments. We then developed a neuromechanical model of hindlimb paw shaking comprised a half-center CPG, activating hip flexors and extensors, and passive viscoelastic distal muscles that produced length/velocity-depended force. Simulations reproduced whip-like mechanisms found experimentally: the proximal-to-distal velocity/acceleration gradient, energy transfer by joint forces and energy absorption by distal muscle moments, as well as atypical co-activation of ankle and hip flexors with knee extensors. Manipulating model parameters, including reversal of segmental inertia distal-to-proximal gradient, demonstrated important inertia contribution to developing the segmental velocity/acceleration proximal-to-distal gradient. We concluded that extreme paw accelerations during paw shaking result from interactions between a spinal CPG, hindlimb segmental inertia, and muscle length/velocity-depended feedback that tunes limb viscoelastic properties.

Mechanisms underlying the activity-dependent regulation of locomotor network performance by the Na+ pump.

Activity-dependent modification of neural network output usually results from changes in neurotransmitter release and/or membrane conductance. In Xenopus frog tadpoles, spinal locomotor network output is adapted by an ultraslow afterhyperpolarization (usAHP) mediated by an increase in Na+ pump current. Here we systematically explore how the interval between two swimming episodes affects the second episode, which is shorter and slower than the first episode. We find the firing reliability of spinal rhythmic neurons to be lower in the second episode, except for excitatory descending interneurons (dINs). The sodium/proton antiporter, monensin, which potentiates Na+ pump function, induced similar effects to short inter-swim intervals. A usAHP induced by supra-threshold pulses reduced neuronal firing reliability during swimming. It also increased the threshold current for spiking and introduced a delay to the first spike in a train, without reducing subsequent firing frequency. This delay was abolished by ouabain or zero K+ saline, which eliminate the usAHP. We present evidence for an A-type K+ current in spinal CPG neurons which is inactivated by depolarization and de-inactivated by hyperpolarization, and accounts for the prolonged delay. We conclude that the usAHP attenuates neuronal responses to excitatory network inputs by both membrane hyperpolarization and enhanced de-inactivation of an A-current.

Electrophysiological representation of scratching CpG activity in the cerebellum.

We analyzed the electrical activity of neuronal populations in the cerebellum and the lumbar spinal cord during fictive scratching in adult decerebrate cats before and after selective sections of the Spino-Reticulo Cerebellar Pathway (SRCP) and the Ventral-Spino Cerebellar Tract (VSCT). During fictive scratching, we found a conspicuous sinusoidal electrical activity, called Sinusoidal Cerebellar Potentials (SCPs), in the cerebellar vermis, which exhibited smaller amplitude in the paravermal and hemisphere cortices. There was also a significant spino-cerebellar coherence between these SCPs and the lumbar sinusoidal cord dorsum potentials (SCDPs). However, during spontaneous activity such spino-cerebellar coherence between spontaneous potentials recorded in the same regions decreased. We found that the section of the SRCP and the VSCT did not abolish the amplitude of the SCPs, suggesting that there are additional pathways conveying information from the spinal CPG to the cerebellum. This is the first evidence that the sinusoidal activity associated to the spinal CPG circuitry for scratching has a broad representation in the cerebellum beyond the sensory representation from hindlimbs previously described. Furthermore, the SCPs represent the global electrical activity of the spinal CPG for scratching in the cerebellar cortex.

Spinal Efference Copy Signaling and Gaze Stabilization during Locomotion in JuvenileXenopusFrogs

In swimming Xenopus laevis tadpoles, gaze stabilization is achieved by efference copies of spinal locomotory CPG output that produce rhythmic extraocular motor activity appropriate for minimizing motion-derived visual disturbances. During metamorphosis, Xenopus switches its locomotory mechanism from larval tail-based undulatory movements to bilaterally synchronous hindlimb kick propulsion in the adult. The change in locomotory mode leads to body motion dynamics that no longer require conjugate left-right eye rotations for effective retinal image stabilization. Using in vivo kinematic analyses, in vitro electrophysiological recordings and specific CNS lesions, we have investigated spino-extraocular motor coupling in the juvenile frog and the underlying neural pathways to understand how gaze control processes are altered in accordance with the animal's change in body plan and locomotor strategy. Recordings of extraocular and limb motor nerves during spontaneous "fictive" swimming in isolated CNS preparations revealed that there is indeed a corresponding change in spinal efference copy control of extraocular motor output. In contrast to fictive larval swimming where alternating bursts occur in bilateral antagonistic horizontal extraocular nerves, during adult fictive limb-kicking, these motor nerves are synchronously active in accordance with the production of convergent eye movements during the linear head accelerations resulting from forward propulsion. Correspondingly, the neural pathways mediating spino-extraocular coupling have switched from contralateral to strictly ipsilateral ascending influences that ensure a coactivation of bilateral extraocular motoneurons with synchronous left-right limb extensions. Thus, adaptive developmental plasticity during metamorphosis enables spinal CPG-driven extraocular motor activity to match the changing requirements for eye movement control during self-motion.

Locomotor network performance controls future network output in Xenopus frog tadpoles

Event Abstract Back to Event Locomotor network performance controls future network output in Xenopus frog tadpoles HongYan Zhang1, Stephen P. Currie1, Laurence Picton1 and Keith T. Sillar1* 1 University of St Andrews, School of Biology, United Kingdom Most rhythm generating neural networks, often called CPGs, produce an output that can vary between two extremes; from fast intense to slow weak activity. How does the relative intensity of network activity influence network performance? We recently described a correlation between the duration of fictive swimming episodes in post-hatchling Xenopus frog tadpoles and the interval from the preceding episode. We reported an underlying minute-long post swim hyperpolarization that involves up-regulation of Na+/K+ pumps. This usAHP acts as a short term memory of CPG performance (Zhang & Sillar, 2012). Here we address in more detail: i) the effect of preceding activity on the basic parameters of swimming; ii) the impact of the usAHP on the firing properties of spinal neurons; and iii) whether the usAHP persists into later stages of development. i) We find that post swim-interval determines the duration of subsequent swim episodes and that short intervals lead to short episodes. During these shortened second episodes swimming occurs at a significantly lower initial frequency and both burst durations and duty cycles are reduced compared to episode 1. ii) Whole cell patch clamp recordings were made from spinal CPG neurons to explore the impact of the usAHP following either swimming or high frequency firing induced by depolarizing current steps. No change in conductance was detected during the usAHP. However, both the amplitude of the action potentials and spike accommodation properties were affected. For example, the delay to the first spike of a train was longer during a usAHP suggesting that SHAL-type voltage-dependent K+ conductances are de-inactivated. iii) Finally we report that the usAHP is present in later free swimming stages; the properties of the usAHP are similar at these stages but it is recorded in a higher proportion of neurons than at earlier stages of development. Acknowledgements Supported by a BBSRC grant (to KTS) and a BBSRC studentship (to SPC). References Zhang, H-Y. & Sillar (2012) Current Biology 22, 526-531. Keywords: Locomotion, modulation, network plasticity, short term memory, sodium pump, Swimming Conference: Tenth International Congress of Neuroethology, College Park. Maryland USA, United States, 5 Aug - 10 Aug, 2012. Presentation Type: Poster (but consider for Participant Symposium) Topic: Motor Systems Citation: Zhang H, Currie SP, Picton L and Sillar KT (2012). Locomotor network performance controls future network output in Xenopus frog tadpoles. Conference Abstract: Tenth International Congress of Neuroethology. doi: 10.3389/conf.fnbeh.2012.27.00114 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 25 Apr 2012; Published Online: 07 Jul 2012. * Correspondence: Prof. Keith T Sillar, University of St Andrews, School of Biology, Scotland, United Kingdom, kts1@st-andrews.ac.uk Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers HongYan Zhang Stephen P Currie Laurence Picton Keith T Sillar Google HongYan Zhang Stephen P Currie Laurence Picton Keith T Sillar Google Scholar HongYan Zhang Stephen P Currie Laurence Picton Keith T Sillar PubMed HongYan Zhang Stephen P Currie Laurence Picton Keith T Sillar Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Reticulospinal neurons controlling forward and backward swimming in the lamprey

Most vertebrates are capable of two forms of locomotion, forward and backward, strongly differing in the patterns of motor coordination. Basic mechanisms generating these patterns are located in the spinal cord; they are activated and regulated by supraspinal commands. In the lamprey, these commands are transmitted by reticulospinal (RS) neurons. The aim of this study was to reveal groups of RS neurons controlling different aspects of forward (FS) and backward (BS) swimming in the lamprey. Activity of individual larger RS neurons in intact lampreys was recorded during FS and BS by chronically implanted electrodes. It was found that among the neurons activated during locomotion, 27% were active only during FS, 3% only during BS, and 70% during both FS and BS. In a portion of RS neurons, their mean firing frequency was correlated with frequency of body undulations during FS (8%), during BS (34%), or during both FS and BS (22%), suggesting their involvement in control of locomotion intensity. RS activity was phasically modulated by the locomotor rhythm during FS (20% of neurons), during BS (29%), or during both FS and BS (16%). The majority of RS neurons responding to vestibular stimulation (and presumably involved in control of body orientation) were active mainly during FS. This explains the absence of stabilization of the body orientation observed during BS. We discuss possible functions of different groups of RS neurons, i.e., activation of the spinal locomotor CPG, inversion of the direction of propagation of locomotor waves, and postural control.

Burst dynamics under mixed NMDA and AMPA drive in the models of the lamprey spinal CPG

The spinal CPG of the lamprey is modeled using a chain of nonlinear oscillators. Each oscillator represents a small neuron population capable of bursting under mixed NMDA and AMPA drive. Parameters of the oscillator are derived from detailed conductance-based neuron models. Analysis and simulations of dynamics of a single oscillator, a chain of locally coupled excitatory oscillators and a chain of two pairs of excitatory and inhibitory oscillators in each segment are done. The roles of asymmetric couplings and additional rostral drive for generation of a traveling wave with one cycle per chain length in a realistic frequency range are studied.

Chapter 8 The spinal locomotor CPG: a target after spinal cord injury

The spinal locomotor circuits depend on a central network often referred as the “central pattern generator network” (CPG), but there is also a powerful sensory component from afferents activated during the locomotor movement. This sensory input influences the duration of the support phase and the degree of muscle activation. In spinal animals, the sensory component is of critical importance and accounts for the fact that spinal animals can adapt to the treadmill speed within a certain range. This chapter extrapolates that the spinal cord of all vertebrates including humans contains the necessary circuitry to provide the basic locomotor coordination. To achieve a dynamic interaction between the brainstem locomotor centers and the spinal cord CPGs, a regeneration of part of the fast reticulospinal glutamatergic axons is required.

Modeling of substance P and 5-HT induced synaptic plasticity in the lamprey spinal CPG: consequences for network pattern generation.

Consequences of synaptic plasticity in the lamprey spinal CPG are analyzed by means of simulations. This is motivated by the effects substance P (a tachykinin) and serotonin (5-hydroxytryptamin; 5-HT) have on synaptic transmission in the locomotor network. Activity-dependent synaptic depression and potentiation have recently been shown experimentally using paired intracellular recordings. Although normally activity-dependent plasticity presumably does not contribute to the patterning of network activity, this changes in the presence of the neuromodulators substance P and 5-HT, which evoke significant plasticity. Substance P can induce a faster and larger depression of inhibitory connections but potentiation of excitatory inputs, whereas 5-HT induces facilitation of both inhibitory and excitatory inputs. Changes in the amplitude of the first postsynaptic potential are also seen. These changes could thus be a potential mechanism underlying the modulatory role these substances have on the rhythmic network activity. The aim of the present study has been to implement the activity dependent synaptic depression and facilitation induced by substance P and 5-HT into two alternative models of the lamprey spinal locomotor network, one relying on reciprocal inhibition for bursting and one in which each hemicord is capable of oscillations. The consequences of the plasticity of inhibitory and excitatory connections are then explored on the network level. In the intact spinal cord, tachykinins and 5-HT, which can be endogenously released, increase and decrease the frequency of the alternating left-right burst pattern, respectively. The frequency decreasing effect of 5-HT has previously been explained based on its conductance decreasing effect on K(Ca) underlying the postspike afterhyperpolarization (AHP). The present simulations show that short-term synaptic plasticity may have strong effects on frequency regulation in the lamprey spinal CPG. In the network model relying on reciprocal inhibition, the observed effects substance P and 5-HT have on network behavior (i.e., a frequency increase and decrease respectively) can to a substantial part be explained by their effects on the total extent and time dynamics of synaptic depression and facilitation. The cellular effects of these substances will in the 5-HT case further contribute to its network effect.

Modeling of plasticity of the synaptic connections in the lamprey spinal CPG — consequences for network behavior

Consequences of synaptic plasticity in the lamprey spinal CPG are analyzed. This is motivated by the experimentally found effects substance P and 5-hydroxytryptamin (5-HT) have on the inhibitory and excitatory synaptic transmission. The effects can be a change of the amplitude of the postsynaptic potentials as well as induction of an activity-dependent facilitation or depression during repetitive activation. Simulations show that network level effects (i.e. swimming frequency) of substance P and 5-HT can to a substantial part be explained based on their effects on the plasticity of the synaptic transmission.

Intersegmental coordination in the lamprey central pattern generator for locomotion

Two theories have been formulated to explain how intersegmental coordination in the lamprey is produced. Both view the spinal locomotor CPG as a chain of coupled oscillators. One involves the development of a general mathematical framework that allows one to examine how differences in the inherent frequencies and differences in the kinds of coupling affect the phase lags along the chain. The other theory suggests a simple way in which constant phase lags along the chain can be produced from a chain in which the first oscillator has an inherently higher frequency and the coupling between oscillators is symmetrical. The goal of this review is to compare the two theories and to evaluate the available experimental data as it relates to both theories.

Vestibular control of swimming in lamprey. I. Responses of reticulospinal neurons to roll and pitch.

A method has been developed for recording the response of single neurons in the lamprey brainstem in vitro to natural stimulation of vestibular receptors. The brainstem dissected together with the intact vestibular apparatus could be rotated in space, in two perpendicular planes (transverse, the roll tilt, and sagittal, the pitch tilt), in one of them up to 360 degrees, and in the other one up to +/- 30 degrees. The responses of single reticulospinal (RS) neurons, in all four reticular nuclei of the brainstem, to roll and pitch were recorded extracellularly and, with small inclinations (up to +/- 45 degrees) also intracellularly. Two types of preparations were used, with and without the rostral part of the spinal cord. In the brainstem preparations, most RS neurons responded both to a definite brain orientation in space and to a change of the orientation (static and dynamic reactions). Responses to roll tilt were similar in all reticular nuclei: all cells were excited with roll tilt towards the contralateral side, this reaction was qualitatively preserved when the roll was performed in combination with different pitch inclinations. Responses to pitch tilt were less clearcut; some neurons were activated with nose-up deflection while others responded to nose-down tilt. In preparations including the spinal cord, responses of RS neurons to roll and pitch tilt differed from those in the isolated brainstem in that they were much less specific and stable. Roll and pitch tilts could trigger the spinal locomotor CPG, which, by sending "efference copy" signals back to the brainstem, produced modulation of RS neurons in relation to the locomotor rhythm.