The locomotor central pattern generator of the rat spinal cord in vitro is optimally activated by noisy dorsal root waveforms

2011 ◽  
Vol 106 (2) ◽  
pp. 872-884 ◽  
Author(s):  
Giuliano Taccola
Keyword(s):  
Spinal Cord ◽  
Electrical Stimulation ◽  
Central Pattern Generator ◽  
Dorsal Root ◽  
Spinal Injury ◽  
Cauda Equina ◽  
Pattern Generator ◽  
Rat Spinal Cord ◽  
Pharmacological Agents

The spinal cord contains an intrinsic locomotor program driven by a central pattern generator that rhythmically activates flexor and extensor limb motor pools. Although long-lasting locomotor activity can be generated pharmacologically, trains of afferent stimuli trigger only few locomotor cycles. The present study investigated whether a new electrical stimulation protocol (termed FL istim) could elicit long-lasting fictive locomotion (FL) in the rat spinal cord in vitro. Thus, after first inducing FL by bath application of N-methyl-d-aspartate and serotonin, the recorded waveform obtained from a lumbar ventral root was digitized and then applied to either a lumbar dorsal root or the cauda equina following washout of pharmacological agents. Two FL istim cycles were the threshold input to evoke an episode of FL from ventral roots. Longer cycles (up to 1 min) induced sustained FL (up to 1 min) with stereotyped periodicity (2.2 ± 0.5 s), despite changing frequency (2–4 s) or cycle amplitude of FL istim. Gradual filtering out of the noise from FL istim trace concomitantly decreased the efficiency of FL so that stimulation with equivalent pure sinusoids produced asynchronous, irregular discharges only that could not be converted to FL by adding spontaneous basal activity. This study is the first demonstration that epochs of rhythmic locomotor-like oscillations applied to a dorsal root represent an efficient stimulus to evoke FL as long as they contain the electrophysiological noise produced within FL cycles. These observations suggest novel strategies to improve the efficiency of electrical stimulation delivered by clinical devices for neurorehabilitation after spinal injury.

scholarly journals Dynamics of episodic and continuous rhythmic activities from a developing central pattern generator

2020 ◽  
Author(s):  
Simon A. Sharples ◽  
Alex Vargas ◽  
Adam P. Lognon ◽  
Leanne Young ◽  
Anchita Shonak ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Central Pattern Generator ◽  
Narrow Range ◽  
Rhythmic Activity ◽  
Pattern Generator ◽  
Newborn Mouse ◽  
Spinal Motor ◽  
State Dependent ◽  
Insight Into

AbstractDeveloping spinal motor networks produce a diverse array of outputs, including episodic and continuous patterns of rhythmic activity. Variation in excitability state and neuromodulatory tone can facilitate transitions between episodic and continuous rhythms; however, the intrinsic mechanisms that govern these rhythms and transitions are poorly understood. Here, we tested the capacity of a single central pattern generator (CPG) circuit with tunable properties to generate multiple outputs. To address this, we deployed a computational model composed of an inhibitory half-centre oscillator. We tested the contributions of key properties predicted by the model to the generation of an episodic rhythm produced by isolated spinal cords of the newborn mouse. The model was capable of reproducing the diverse state-dependent rhythms evoked by dopamine in the neonatal mouse spinal cord. In the model, episodic bursting depended predominantly on the endogenous oscillatory properties of neurons, with persistent Na+(INaP), Na+-K+ ATPase pump (IPump), and hyperpolarization-activated currents (Ih) playing key roles. Modulation of all three currents produced transitions between episodic and continuous rhythms and silence. Pharmacological manipulation of these properties in vitro led to consistent changes in spinally generated rhythmic outputs elicited by dopamine. The model also showed multistable zones within a narrow range of parameter space for IPump and Ih, where switches between rhythms were rapidly triggered by brief but specific perturbations. Outside of those zones, brief perturbations could reset episodic and continuous rhythmicity generated by the model. Our modelling and experimental results provide insight into mechanisms that govern the generation of multiple patterns of rhythmicity by a single CPG. We propose that neuromodulators alter circuit properties to position the network within regions of state-space that favour stable outputs or, in the case of multistable zones, facilitate rapid transitions between states.Significance statementThe ability of a single CPG to produce and transition between multiple rhythmic patterns of activity is poorly understood. We deployed a complementary computational half-centre oscillator model and an isolated spinal cord experimental model to identify key currents whose interaction produced episodic and continuous rhythmic activity. Combined, our experimental and modelling approaches suggest mechanisms that govern generating and transitioning between diverse rhythms in mammalian spinal networks. This work sheds light on the ability of a single CPG to produce episodic bouts often observed in behavioural contexts.

Coapplication of noisy patterned electrical stimuli and NMDA plus serotonin facilitates fictive locomotion in the rat spinal cord

2012 ◽  
Vol 108 (11) ◽  
pp. 2977-2990 ◽  
Author(s):  
Francesco Dose ◽  
Giuliano Taccola
Keyword(s):  
Spinal Cord ◽  
Fictive Locomotion ◽  
Rat Spinal Cord ◽  
High Potassium ◽  
Pharmacological Agents ◽  
Afferent Fibers ◽  
Locomotor Patterns ◽  
Vitro Model

A new stimulating protocol [fictive locomotion-induced stimulation (FL istim)], consisting of intrinsically variable weak waveforms applied to a single dorsal root is very effective (though not optimal as it eventually wanes away) in activating the locomotor program of the isolated rat spinal cord. The present study explored whether combination of FL istim with low doses of pharmacological agents that raise network excitability might further improve the functional outcome, using this in vitro model. FL istim was applied together with N-methyl-d-aspartate (NMDA) + serotonin, while fictive locomotion (FL) was electrophysiologically recorded from lumbar ventral roots. Superimposing FL istim on FL evoked by these neurochemicals persistently accelerated locomotor-like cycles to a set periodicity and modulated cycle amplitude depending on FL istim rate. Trains of stereotyped rectangular pulses failed to replicate this phenomenon. The GABAB agonist baclofen dose dependently inhibited, in a reversible fashion, FL evoked by either FL istim or square pulses. Sustained episodes of FL emerged when FL istim was delivered, at an intensity subthreshold for FL, in conjunction with subthreshold pharmacological stimulation. Such an effect was, however, not found when high potassium solution instead of NMDA + serotonin was used. These results suggest that the combined action of subthreshold FL istim (e.g., via epidural stimulation) and neurochemicals should be tested in vivo to improve locomotor rehabilitation after injury. In fact, reactivation of spinal locomotor circuits by conventional electrical stimulation of afferent fibers is difficult, while pharmacological activation of spinal networks is clinically impracticable due to concurrent unwanted effects. We speculate that associating subthreshold chemical and electrical inputs might decrease side effects when attempting to evoke human locomotor patterns.

Rostral Versus Caudal Differences in Mechanical Entrainment of the Lamprey Central Pattern Generator for Locomotion

2008 ◽  
Vol 99 (5) ◽  
pp. 2408-2419 ◽  
Author(s):  
Eric D. Tytell ◽  
Avis H. Cohen
Keyword(s):  
Spinal Cord ◽  
Central Pattern Generator ◽  
Muscle Activity ◽  
Pattern Generator ◽  
The Body ◽  
Phase Lag ◽  
Neural Basis ◽  
Phase Gradient

In fishes, undulatory swimming is produced by sets of spinal interneurons constituting a central pattern generator (CPG). The CPG generates waves of muscle activity that travel from head to tail, which then bend the body into wave shapes that also travel from head to tail. In many fishes, the wavelengths of the neural and mechanical waves are different, resulting in a rostral-to-caudal gradient in phase lag between muscle activity and bending. The neural basis of this phase gradient was investigated in the lamprey spinal cord using an isolated in vitro preparation. Fictive swimming was induced using d-glutamate and the output of the CPG was measured using suction electrodes placed on the ventral roots. The spinal cord was bent sinusoidally at various points along its length. First, the ranges of entrainment were estimated. Middle segments were able to entrain to frequencies approximately twice as high as those at end segments. Next, phase lags between centers of ventral root bursts and the stimulus were determined. Two halves of the cycle were identified: stretching and shortening of the edge of spinal cord on the same side as the electrode. Stimuli at rostral segments tended to entrain segmental bursting at the beginning of the stretch phase, almost 50% out of phase with previously measured in vivo electromyography data. Stimuli at caudal segments, in contrast, entrained segments at the end of stretch and the beginning of shortening, approximately the same phase as in vivo data.

scholarly journals Serotonin modulates the central pattern generator for locomotion in the isolated lamprey spinal cord

1985 ◽  
Vol 116 (1) ◽  
pp. 27-46 ◽  
Author(s):  
R. M. Harris-Warrick ◽  
A. H. Cohen
Keyword(s):  
Spinal Cord ◽  
Central Pattern Generator ◽  
Experimental Studies ◽  
Input Resistance ◽  
Pattern Generator ◽  
Resting Potential ◽  
Phase Lag ◽  
Burst Discharge ◽  
Swimming Pattern

The central pattern generator for locomotion in the spinal cord of the lamprey can be activated in vitro by the addition of D-glutamate to the bathing saline. Serotonin has no effects when bath-applied alone, but it modulates the D-glutamate-activated swimming pattern. Three major effects are observed: a dose-dependent reduction in the frequency of rhythmic ventral root burst discharge; enhancement of the intensity of burst discharge, due in part to the recruitment of previously inactive motoneurones; prolongation of the intersegmental phase lag. Motoneurone activation appears to result from enhanced synaptic drive from the central pattern generator; no direct effects of serotonin on the motoneurones themselves (resting potential, input resistance or threshold for action potential generation) were observed. Theoretical and experimental studies suggest that the prolongation of the intersegmental phase lag results at least in part from differential effects of serotonin on segmental oscillators in different parts of the spinal cord. Isolated caudal pieces of the cord were more strongly affected by serotonin than isolated rostral pieces. We propose that serotonin may be an endogenous modulator of the central pattern generator for locomotion in the lamprey. It may have a role in the generation of a family of related undulatory movements (swimming, crawling, burrowing) by a single central pattern generator.

Neuronal Bursting Induced by NK3 Receptor Activation in the Neonatal Rat Spinal Cord In Vitro

2001 ◽  
Vol 86 (6) ◽  
pp. 2939-2950 ◽  
Author(s):  
Cristina Marchetti ◽  
Andrea Nistri
Keyword(s):  
Spinal Cord ◽  
Membrane Potential ◽  
Dorsal Root ◽  
Extracellular Recording ◽  
Rhythmic Activity ◽  
Input Resistance ◽  
Receptor Activation ◽  
Neonatal Rat ◽  
Rat Spinal Cord

Intracellular recording from lumbar motoneurons and extracellular recording from ventral roots of the neonatal rat isolated spinal cord were used to study the mechanisms responsible for the excitation mediated by NK3 tachykinin receptors. The selective NK3 agonists senktide or [MePhe7]neurokinin B induced a slow depolarization with superimposed oscillations (mean period ± SD was 2.8 ± 0.8 s) that, in the majority of cases, showed left-right alternation at segmental level and were synchronous between L2 and L5 of the same side. During agonist wash out (5–20 min) a delayed form of hyperexcitability emerged consisting of bursts lasting 8 ± 2 s (average interburst interval 55 ± 21 s) with superimposed oscillations usually with homosegmental alternation and heterosegmental synchronicity. Such bursting was accompanied by depression of GABAergic dorsal root potentials evoked by dorsal root stimulation and of the recurrent inhibitory postsynaptic potential recorded from motoneurons. Despite bursting, motoneuron membrane potential returned to baseline while input resistance was increased. Bursts were a network-dependent phenomenon triggered by previous NK3 receptor activation because bursting was suppressed by glutamate receptor antagonists and was insensitive to motoneuron membrane potential or subsequent application of an NK3 receptor antagonist. NK3 receptors operated synergistically with N-methyl-d-aspartate (NMDA) and 5-hydroxytryptamine (5-HT) to trigger fully alternating locomotor-like rhythms while NK3 receptor antagonism disrupted the same rhythm. In summary, in the neonatal rat spinal cord NK3 receptors could trigger rhythmic activity predominantly with alternation at segmental level but with synchronous coupling between ipsilateral motor pools. NK3receptor activation could also facilitate fictive locomotor patterns induced by NMDA and 5-HT.

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