Characteristics of the electrical oscillations evoked by 4-aminopyridine on dorsal root fibers and their relation to fictive locomotor patterns in the rat spinal cord in vitro

Neuroscience ◽  
2005 ◽  
Vol 132 (4) ◽  
pp. 1187-1197 ◽  
Author(s):  
G. Taccola ◽  
A. Nistri
Keyword(s):  
Spinal Cord ◽  
Dorsal Root ◽  
Rat Spinal Cord ◽  
Locomotor Patterns

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.

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.

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.

Depression of Windup of Spinal Neurons in the Neonatal Rat Spinal Cord In Vitro by an NK3 Tachykinin Receptor Antagonist

2001 ◽  
Vol 85 (4) ◽  
pp. 1502-1511 ◽  
Author(s):  
Mario Barbieri ◽  
Andrea Nistri
Keyword(s):  
Spinal Cord ◽  
Synaptic Transmission ◽  
Receptor Antagonist ◽  
Dorsal Root ◽  
Direct Action ◽  
Extracellular Recording ◽  
Neonatal Rat ◽  
Rat Spinal Cord ◽  
Tachykinin Receptor

The effects of the NK3 tachykinin receptor antagonist SR 142801 on synaptic transmission and spike windup induced by trains of stimuli applied to a dorsal root were investigated with intra- and extracellular recording from the neonatal rat spinal cord in vitro. SR 142801 (10 μM) reduced the depolarization (recorded from lumbar ventral roots) induced by senktide (an NK3 agonist) more strongly than the one evoked by substance P methyl ester (SPMeO; an NK1 agonist). Nevertheless, after a long (>2 h) application time, SR 142801 largely depressed the response to SPMeO as well. When NK1 or NK3 receptors were blocked by >50% in the presence of SR 142801, there was also a significant reduction in the cumulative depolarization induced by repeated stimuli to a single dorsal root. This blocking action by SR 142801 was also observed in the presence of the N-methyl-d-aspartate (NMDA) receptor antagonist d-aminophosphonovalerate (APV) and the calcium channel blocker nifedipine. Intracellular data from lumbar motoneurons showed that the spike windup was the first and most sensitive target for the SR 142801 blocking effect. Increasing stimulus strength to dorsal root fibers could partly surmount such a block. SR 142801 per se had no direct action on fast synaptic transmission, membrane potential, or input resistance. These findings indicate that SR 142801 could lead to an early, large reduction in the windup of action potential discharge by motoneurons, suggesting its ability to suppress the reflex component of central sensitization evoked by repeated dorsal root stimuli.

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