Absence Of Supraspinal Control Research Articles

Rhythmogenic networks are potently modulated by activation of muscarinic acetylcholine receptors in the rodent spinal cord.

Electrical stimulation of the spinal cord is a potent means for activating mammalian stepping in the absence of the descending control from the brain. Previously, we have shown that stimulation of pain delivering (Aδ) sacrocaudal afferents (SCA) has a powerful capacity to activate the sacral and lumbar rhythmogenic networks in the neonatal rodent spinal cord. Relatively little is known about the neural pathways involved in activation of the locomotor networks by Aδ afferents, on their mechanism of action and on the possibility to modulate their activity. We have shown that elevation of the endogenous level of acetylcholine at the sacral cord by blocking cholinesterase could modulate the SCA-induced locomotor rhythm in a muscarinic receptor-dependent mechanism. Here, we review these and more recent findings and report that controlled stimulation of SCA in the presence of muscarine is a potent activator of the locomotor network. The possible mechanisms involved in the muscarinic modulation of the locomotor rhythm are discussed in terms of the differential projections of sacral relay neurons, activated by SCA stimulation, to the lumbar locomotor rhythm generators, and to their target motoneurons. Altogether, our studies show that manipulations of cholinergic networks offer a simple and powerful means to control the activity of locomotor networks in the absence of supraspinal control. Cover Image for this issue: https://doi.org/10.1111/jnc.15079.

Ascending pathways that mediate cholinergic modulation of lumbar motor activity.

Deciphering neuronal pathways that reactivate spinal central pattern generators (CPGs) and modulate the activity of spinal motoneurons in mammals in the absence of supraspinal control is important for understanding of neural control of movement and for developing novel therapeutic approaches to improve the mobility of spinal cord injury patients. Previously, we showed that the sacral and lumbar cholinergic system could potently modulate the locomotor CPGs in newborn rodents. Here, we review these and our more recent studies of sacral relay neurons with lumbar projections to the locomotor CPGs and to lumbar motoneurons and demonstrate that sacral and lumbar cholinergic components have the capacity to control the frequency of the locomotor CPGs and at the same time the motor output of the activated lumbar motoneurons during motor behavior. A model describing the suggested ascending sacro-lumbar connectivity involved in modulation of the locomotor rhythm by sacral cholinergic components is proposed and discussed. This is an article for thespecial issue XVth International Symposium on Cholinergic Mechanisms.

Long and Short Multifunicular Projections of Sacral Neurons Are Activated by Sensory Input to Produce Locomotor Activity in the Absence of Supraspinal Control

Afferent input from load and joint receptors has been shown to reactivate the central pattern generators for locomotion (CPGs) in spinal cord injury patients and thereby improve their motor function and mobility. Elucidation of the pathways interposed between the afferents and CPGs is critical for the determination of the capacity of sensory input to activate the CPGs when the continuity of the white matter tracts is impaired following spinal cord injury. Using electrophysiological recordings, confocal imaging studies of spinal neurons and surgical manipulations of the white matter, we show that the capacity of sacrocaudal afferent (SCA) input to produce locomotor activity in isolated rat spinal cords depends not only on long ascending pathways, but also on recruitment of sacral proprioneurons interposed between the second order neurons and the hindlimb CPGs. We argue that large heterogeneous populations of second-order and proprioneurons whose crossed and uncrossed axons project rostrally through the ventral, ventrolateral/lateral and dorsolateral white matter funiculi contribute to the generation of the rhythm by the stimulated sacrocaudal input. The complex organization and multiple projection patterns of these populations enable the sacrocaudal afferent input to activate the CPGs even if the white matter pathways are severely damaged. Further studies are required to clarify the mechanisms involved in SCA-induced locomotor activity and assess its potential use for the rescue of lost motor functions after spinal cord injury.

Sensory‐induced activation of pattern generators in the absence of supraspinal control

Sacrocaudal afferent (SCA) stimulation is used in this work to study neural pathways involved in sensory-activation of central pattern generators (CPGs) in the isolated spinal cord of the neonatal rat. Surgical manipulations of the white matter funiculi and confocal imaging of back-labeled funicular pathways suggest that the CPGs are activated during SCA stimulation by crossed and uncrossed multifunicular projections of sacral neurons and that activation of short projecting proprioneurons is sufficient for the generation of the rhythm by SCA stimulation. The versatile organization of the pathways involved in the SCA-induced rhythm makes it a potent and durable activator of the CPGs in the absence of descending control from the brain. The significance of our findings and their potential clinical use are discussed.

Cardiovascular responses during arm exercise and orthostatic challenge in individuals with paraplegia.

In this study the cardiorespiratory responses during arm crank ergometry (ACE) performed at two submaximal intensities (30% and 50% of heart rate reserve) and moderate orthostatic challenge were investigated in individuals with paraplegia (PARA). The effect of concurrent electrical stimulation (ES)-induced leg muscle contractions on the responses to ACE during orthostatic challenge was also investigated. Eight PARA (T5-T12) and eight able-bodied (AB) individuals participated in this study, however only seven subjects from each group completed all tests and were used in subsequent data analyses. Oxygen uptake (VO2), heart rate (fc), stroke volume (SV) and cardiac output (Qc) were assessed during (1) ACE alone, (2) ACE and lower body negative pressure (ACE + LBNP), and, in PARA only, (3) ACE + LBNP with ES (ACE + LBNP+ ES). In both PARA and AB, ACE + LBNP decreased SV (by 13-18% and 20-23%, respectively) and increased fc (by 13-15% and 16%, respectively) compared to ACE alone. The decrease in SV was greater in AB than in PARA (significant group x trial interaction; both ACE intensities pooled), but there was no difference in the magnitude of increase in fc between groups. ES-induced leg muscle contractions increased SV (up to 16%) but did not change VO2 or Qc. The smaller reduction in SV from ACE to ACE + LBNP in PARA may indicate a mechanism by which adequate central blood volume can be maintained in the face of orthostatic challenge, despite the absence of supraspinal control below the spinal cord lesion. With ES-induced leg muscle contractions, the decrease in SV, which occurred during ACE + LBNP, was reversed via reactivation of the lower limb muscle pump and augmented venous return.

Effects of spinal transection in neonatal and weanling rats: Survival of function

The spinal cord of neonatal rats and weanling rats was transected midthoracically. The recovery and maturation of responses in the hind quarters were followed and compared with response development in normal rats. In rats transected as neonates, the hind limbs supported the hind quarters, the tail was dorsiflexed, and the hind limbs stepped during locomotion. When a hind limb fell through a grid, struggling movements, replacement, and a response similar to tactile placing were observed. Rapid extension often bounced the hind quarters off a grid when the foot pads contacted a grid bar. Pinching elicited clonic flexion and wriggling of the hind quarters with a prolonged afterdischarge. In animals transected as weanlings, the hind limbs and tail were passively extended and did not participate in locomotion. The hind limbs also hung passively through a grid and struggling was brief. Clonic flexion and wriggling to pinch lacked an afterdischarge. Choreoathetoidlike movements and spasms were common in the weanling group. In a number of respects including temporal correspondence in the appearance of certain responses, the response maturation of the neonatally transected animal resembled the ontogeny of responses in the normal animal. These data indicate that the local development of the spinal cord continues in the absence of supraspinal control. Hence it appears that the presence or absence of supraspinal control during development is the basis for the differences in the survival of responses from the isolated spinal cords of the neonatal group when compared to the weanling animals. This “survival of function” effect may help to explain the sparing of function often found after lesions in the developing nervous system.