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

Abstract

, 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 FListim with low doses of pharmacological agents that raise network excitability might further improve the functional outcome, using this in vitro model. FListim was applied together with N-methyl-D-aspartate (NMDA) ϩ serotonin, while fictive locomotion (FL) was electrophysiologically recorded from lumbar ventral roots. Superimposing FListim on FL evoked by these neurochemicals persistently accelerated locomotorlike cycles to a set periodicity and modulated cycle amplitude depending on FListim rate. Trains of stereotyped rectangular pulses failed to replicate this phenomenon. The GABA B agonist baclofen dose dependently inhibited, in a reversible fashion, FL evoked by either FListim or square pulses. Sustained episodes of FL emerged when FListim 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 ϩ serotonin was used. These results suggest that the combined action of subthreshold FListim (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. fictive locomotion; central pattern generator; dorsal root train; FListim IN THE ISOLATED SPINAL CORD of the neonatal rat, episodes of locomotor-like oscillations can be recorded from lumbar (L) 2 and L5 ventral roots (VRs), alternating between the left and right sides of the cord, due to rhythmic activation of flexor and extensor motor pools, respectively

Nanomolar Oxytocin Synergizes with Weak Electrical Afferent Stimulation to Activate the Locomotor CPG of the Rat Spinal Cord In Vitro

“…8 shows one example taken from the same preparation tested with various protocols. Thus, the FL i stim protocol (duration  =  60 s, intensity  =  0.2×Th) [37], [39] was first applied to a sacral DR, inducing a cumulative depolarization with superimposed an episode of alternating cycles on L2 and L5 VRs (on both sides), lasting throughout the delivery of the stimulating pattern (Fig. 8 A).…”

“…Furthermore, FL i stim, as opposed to trains of pulses traditionally delivered to dorsal afferents, synergizes with sub-threshold concentrations of N-methyl-D-aspartate (NMDA) and serotonin (5-hydroxytryptamine, 5HT) to activate the CPG [39]. Using the in vitro rat spinal cord, the present study aims at exploring whether the neuropeptide could facilitate the effects of FL i stims, comparing it with chemically-evoked FL, and relating to its actions of synaptic transmission, network rhythmicity induced by pharmacological disinhibition [40] and motoneuron properties.…”

Rat locomotor spinal circuits in vitro are activated by electrical stimulation with noisy waveforms sampled from human gait

“…In fact, an epoch of FL analogous for duration and number of oscillations to the one evoked by ReaL i stim has been previously observed with FL i stim elicited by NMDA + 5‐HT (Taccola ; Dose and Taccola ).…”

“…This special stimulation pattern, even when applied at amplitude lower than the one required by standard square pulses, was able to induce locomotor‐like oscillations of longer duration and with a greater number of cycles than hitherto described (Taccola ). The specific recruitment of the locomotor central pattern generator (CPG) made by FL i stim is confirmed by its ability to synergize the FL induced by NMDA (N‐Methyl‐D‐aspartate) + 5‐HT (5‐hydroxytryptamine; Dose and Taccola ). Although the precise mechanisms through which FL i stim can activate locomotor CPG remain unclear, its intrinsic noise turns out to be a crucial feature (Taccola ).…”

Accelerating locomotor recovery after incomplete spinal injury

“…In addition to the repetitive motion therapies discussed below, a large number of different types of therapy have been attempted for spinal cord injury. These include the application of transplants and neurotrophic factors, viral vectors, neural bypasses, and combinations of treatments …”