Neurophysiology of epidurally evoked spinal cord reflexes in clinically motor-complete posttraumatic spinal cord injury

Increased use of epidural Spinal Cord Stimulation (eSCS) for the rehabilitation of spinal cord injury (SCI) has highlighted the need for a greater understanding of the properties of reflex circuits in the isolated spinal cord, particularly in response to repetitive stimulation. Here, we investigate the frequency-dependence of modulation of short- and long-latency EMG responses of lower limb muscles in patients with SCI at rest. Single stimuli could evoke short-latency responses as well as long-latency (likely polysynaptic) responses. The short-latency component was enhanced at low frequencies and declined at higher rates. In all muscles, the effects of eSCS were more complex if polysynaptic activity was elicited, making the motor output become an active process expressed either as suppression, tonic or rhythmical activity. The polysynaptic activity threshold is not constant and might vary with different stimulation frequencies, which speaks for its temporal dependency. Polysynaptic components can be observed as direct responses, neuromodulation of monosynaptic responses or driving the muscle activity by themselves, depending on the frequency level. We suggest that the presence of polysynaptic activity could be a potential predictor for appropriate stimulation conditions. This work studies the complex behaviour of spinal circuits deprived of voluntary motor control from the brain and in the absence of any other inputs. This is done by describing the monosynaptic responses, polysynaptic activity, and its interaction through its input–output interaction with sustain stimulation that, unlike single stimuli used to study the reflex pathway, can strongly influence the interneuron circuitry and reveal a broader spectrum of connectivity.

Plasticity of Spinal Cord Reflexes After a Complete Transection in Adult Rats: Relationship to Stepping Ability

Changes in epidurally induced (S1) spinal cord reflexes were studied as a function of the level of restoration of stepping ability after spinal cord transection (ST). Three types of responses were observed. The early response (ER) had a latency of 2.5 to 3 ms and resulted from direct stimulation of motor fibers or motoneurons. The middle response (MR) had a latency of 5 to 7 ms and was monosynaptic. The late response (LR) had a latency of 9 to 11 ms and was polysynaptic. After a complete midthoracic ST, the LR was abolished, whereas the MR was facilitated and progressively increased. The LR reappeared about 3 wk after ST and increased during the following weeks. Restoration of stepping induced by epidural stimulation at 40 Hz coincided with changes in the LR. During the first 2 wk post-ST, rats were unable to step and electrophysiological assessment failed to show any LR. Three weeks post-ST, epidural stimulation resulted in a few steps and these coincided with reappearance of the LR. The ability of rats to step progressively improved from wk 3 to wk 6 post-ST. There was a continuously improved modulation of rhythmic EMG bursts that was correlated with restoration of the LR. These results suggest that restoration of polysynaptic spinal cord reflexes after complete ST coincides with restoration of stepping function when facilitated by epidural stimulation. Combined, these findings support the view that restoration of polysynaptic spinal cord reflexes induced epidurally may provide a measure of functional restoration of spinal cord locomotor networks after ST.

Neuropeptide-Mediated Facilitation and Inhibition of Sensory Inputs and Spinal Cord Reflexes in the Lamprey

Neuropeptide-mediated facilitation and inhibition of sensory inputs and spinal cord reflexes in the lamprey. The effects of neuromodulators present in the dorsal horn [tachykinins, neuropeptide Y (NPY), bombesin, and GABAB agonists] were studied on reflex responses evoked by cutaneous stimulation in the lamprey. Reflex responses were elicited in an isolated spinal cord preparation by electrical stimulation of the attached tail fin. To be able to separate modulator-induced effects at the sensory level from that at the motor or premotor level, the spinal cord was separated into three pools with Vaseline barriers. The caudal pool contained the tail fin. Neuromodulators were added to this pool to modulate sensory inputs evoked by tail fin stimulation. The middle pool contained high divalent cation or low calcium Ringer to block polysynaptic transmission and thus limit the input to the rostral pool to that from ascending axons that project through the middle pool. Ascending inputs and reflex responses were monitored by making intracellular recordings from motor neurons and extracellular recordings from ventral roots in the rostral pool. The tachykinin neuropeptide substance P, which has previously been shown to potentiate sensory input at the cellular and synaptic levels, facilitated tail fin-evoked synaptic inputs to neurons in the rostral pool and concentration dependently facilitated rostral ventral root activity. Substance P also facilitated the modulatory effects of tail fin stimulation on ongoing locomotor activity in the rostral pool. In contrast, NPY and the GABAB receptor agonist baclofen, both of which have presynaptic inhibitory effects on sensory afferents, reduced the strength of ascending inputs and rostral ventral root responses. We also examined the effects of the neuropeptide bombesin, which is present in sensory axons, at the cellular, synaptic, and reflex levels. As with substance P, bombesin increased tail fin stimulation-evoked inputs and ventral root responses in the rostral pool. These effects were associated with the increased excitability of slowly adapting mechanosensory neurons and the potentiation of glutamatergic synaptic inputs to spinobulbar neurons. These results show the possible behavioral relevance of neuropeptide-mediated modulation of sensory inputs at the cellular and synaptic levels. Given that the types and locations of neuropeptides in the dorsal spinal cord of the lamprey show strong homologies to that of higher vertebrates, these results are presumably relevant to other vertebrate systems.