Stimulation Of Hindlimb Nerves Research Articles

Characterisation and functional mapping of surface potentials in the rat dorsal column nuclei.

The brainstem dorsal column nuclei (DCN) process sensory information arising from the body before it reaches the brain and becomes conscious. Despite significant investigations into sensory coding in peripheral nerves and the somatosensory cortex, little is known about how sensory information arising from the periphery is represented in the DCN. Following stimulation of hind-limb nerves, we mapped and characterised the evoked electrical signatures across the DCN surface. We show that evoked responses recorded from the DCN surface are highly reproducible and are unique to nerves carrying specific sensory information. The brainstem dorsal column nuclei (DCN) play a role in early processing of somatosensory information arising from a variety of functionally distinct peripheral structures, before being transmitted to the cortex via the thalamus. To improve our understanding of how sensory information is represented by the DCN, we characterised and mapped low- (<200Hz) and high-frequency (550-3300Hz) components of nerve-evoked DCN surface potentials. DCN surface potentials were evoked by electrical stimulation of the left and right nerves innervating cutaneous structures (sural nerve), or a mix of cutaneous and deep structures (peroneal nerve), in 8-week-old urethane-anaesthetised male Wistar rats. Peroneal nerve-evoked DCN responses demonstrated low-frequency events with significantly longer durations, more high-frequency events and larger magnitudes compared to responses evoked from sural nerve stimulation. Hotspots of low- and high-frequency DCN activity were found ipsilateral to stimulated nerves but were not symmetrically organised. In conclusion, we find that sensory inputs from peripheral nerves evoke unique and characteristic DCN activity patterns that are highly reproducible both within and across animals.

Responses of vestibular nucleus neurons to inputs from the hindlimb are enhanced following a bilateral labyrinthectomy.

Vestibular nucleus neurons have been shown to respond to stimulation of afferents innervating the limbs. However, a limitation in the potential translation of these findings is that they were obtained from decerebrate or anesthetized animals. The goal of the present study was to determine whether stimulation of hindlimb nerves similarly affects vestibular nucleus neuronal activity in conscious cats, and whether the responsiveness of neurons to the stimuli is altered following a bilateral labyrinthectomy. In labyrinth-intact animals, the firing rate of 24/59 (41%) of the neurons in the caudal vestibular nucleus complex was affected by hindlimb nerve stimulation. Most responses were excitatory; the median response latency was 20 ms, but some units had response latencies as short as 10 ms. In the first week after a bilateral labyrinthectomy, the proportion of vestibular nucleus neurons that responded to hindlimb nerve stimulation increased slightly (to 24/55 or 44% of units). However, during the subsequent postlabyrinthectomy survival period, the proportion of vestibular nucleus neurons with hindlimb inputs increased significantly (to 30/49 or 61% of units). Stimuli to hindlimb nerves needed to elicit neuronal responses was consistently over three times the threshold for eliciting an afferent volley. These data show that inputs from hindlimb afferents smaller than those innervating muscle spindles and Golgi tendon organs affect the processing of information in the vestibular nuclei, and that these inputs are enhanced following a bilateral labyrinthectomy. These findings have implications for the development of a limb neuroprosthetics device for the management of bilateral vestibular loss.

Coordinated, multi-joint, fatigue-resistant feline stance produced with intrafascicular hind limb nerve stimulation

The production of graceful skeletal movements requires coordinated activation of multiple muscles that produce torques around multiple joints. The work described herein is focused on one such movement, stance, that requires coordinated activation of extensor muscles acting around the hip, knee and ankle joints. The forces evoked in these muscles by external stimulation all have a complex dependence on muscle length and shortening velocities, and some of these muscles are biarticular. In order to recreate sit-to-stand maneuvers in the anesthetized feline, we excited the hind limb musculature using intrafascicular multielectrode stimulation (IFMS) of the muscular branch of the sciatic nerve, the femoral nerve and the main branch of the sciatic nerve. Stimulation was achieved with either acutely or chronically implanted Utah Slanted Electrode Arrays (USEAs) via subsets of electrodes (1) that activated motor units in the extensor muscles of the hip, knee and ankle joints, (2) that were able to evoke large extension forces and (3) that manifested minimal coactivation of the targeted motor units. Three hind limb force-generation strategies were investigated, including sequential activation of independent motor units to increase force, and interleaved or simultaneous IFMS of three sets of six or more USEA electrodes that excited the hip, knee and ankle extensors. All force-generation strategies evoked stance, but the interleaved IFMS strategy also reduced muscle fatigue produced by repeated sit-to-stand maneuvers compared with fatigue produced by simultaneous activation of different motor neuron pools. These results demonstrate the use of interleaved IFMS as a means to recreate coordinated, fatigue-resistant multi-joint muscle forces in the unilateral hind limb. This muscle activation paradigm could provide a promising neuroprosthetic approach for the restoration of sit-to-stand transitions in individuals who are paralyzed by spinal cord injury, stroke or disease.

Patterning of somatosympathetic reflexes

In a previous study, we reported that vestibular nerve stimulation in the cat elicits a specific pattern of sympathetic nerve activation, such that responses are particularly large in the renal nerve. This patterning of vestibulosympathetic reflexes was the same in anesthetized and decerebrate preparations. In the present study, we report that inputs from skin and muscle also elicit a specific patterning of sympathetic outflow, which is distinct from that produced by vestibular stimulation. Renal, superior mesenteric, and lumbar colonic nerves respond most strongly to forelimb and hindlimb nerve stimulation (approximately 60% of maximal nerve activation), whereas external carotid and hypogastric nerves were least sensitive to these inputs (approximately 20% of maximal nerve activation). In contrast to vestibulosympathetic reflexes, the expression of responses to skin and muscle afferent activation differs in decerebrate and anesthetized animals. In baroreceptor-intact animals, somatosympathetic responses were strongly attenuated (to <20% of control in every nerve) by increasing blood pressure levels to >150 mmHg. These findings demonstrate that different types of somatic inputs elicit specific patterns of sympathetic nerve activation, presumably generated through distinct neural circuits.

No Neuronal Regulation of Murine Bone Marrow Function

AbstractBone marrow is innervated by efferent (sympathetic) and afferent nerves, but it is not clear whether these nerves affect cell formation or release in any significant way. To elucidate this problem, we studied mice neonatally sympathectomized with 6-hydroxydopamine and adult mice in which one hind limb was surgically denervated. Progenitor and transit cell numbers and proliferative activity were estimated in bone marrow, blood, and spleen. In addition, we performed unilateral electrical stimulation of nerve fibers to tibial marrow and applied a cell mobilizing stimulus (bleeding, granulocyte colony-stimulating factor injection, or intraperitoneal injection of a chemotactic substance) to investigate cell egress from the marrow. Blood flow to hindleg bone marrow was assessed with the radioactive microsphere technique. Except for a smaller bone marrow cell population and lower body weight in neonatally sympathectomized mice, we found no clear indications that bone marrow innervation influenced cell production. Also, the innervation did not detectably affect cell release from the marrow. Electrical stimulation of hind limb nerves did not change the blood flow to the marrow, whereas it markedly decreased blood flow to the overlying muscle. We therefore conclude that no obvious function can be ascribed to tibial marrow innervation in the mouse.

Afferent control of central pattern generators: Experimental analysis of locomotion in the decerebrate cat

Changes in the motor activity of the spinal locomotor generator evoked by tonic and phasic peripheral afferent signals during fictitious locomotion of both slow and fast rhythms were analysed in the cat. The tonic afferent inflow was conditioned by the position of the hindlimb. The phasic afferent signals were imitated by electrical stimulation of hindlimb nerves. The correlation between the kinematics of hindlimb locomotor movement and sensory inflow was investigated during actual locomotion. Reliable correlations between motor activity parameters during fictitious locomotion were revealed in cases of both slow and fast “locomotor” rhythms. The main difference between these cases was that correlations “duration-intensity” were positive in the first and negative in the second case. The functional role of “locomotor” pattern dependence on tonic sensory inflow consisted of providing stability for planting the hindlimb on the ground. For any investigated afferent input the phase moments in the “locomotor” cycle were found, in which an afferent signal caused no rearrangement in locomotor generator activity. These moments corresponded to the transitions between “flexion” and “extension” phases and to the bursts of integral afferent activity observed during real locomotion. The data obtained are compared with the results previously described for the scratching generator. The character of changes in “locomotor” activity in response to tonic and phasic sensory signals was similar to that of such changes in “scratching” rhythm in the case of fast “locomotion”. Intensification of the “flexion” phase caused by phasic high-intensity stimulation of cutaneous afferents during low “locomotor” rhythm was changed to inhibition (such as observed during “scratching”) when this rhythm was fast. It is concluded that the main regularities of peripheral afferent control for both the locomotor and scratching generators are the same. Moreover, these central pattern generators are just working regimes of a general spinal motor optimal control system containing the intrinsic model of limb movement dynamics. The consequences of this concept and ways of further research are discussed.

Inhibition of nociceptive neuronal responses in the cat's spinal dorsal horn by electrical stimulation and morphine microinjection in nucleus raphe magnus

The descending inhibitions produced by morphine microinjection and electrical stimulation in the nucleus raphe magnus (NRM) on dorsal horn neurons excited by noxious heating of the skin and/or electrical stimulation of hind limb nerves were examined in the cat. The responses to A-volleys were inhibited to 60.1% (mean, n = 9), those to C-volleys to 64.8% of control (mean, n = 6) and responses to skin heating to 25.3% (mean, n = 8) by electrical NRM stimulation. Morphine (e.g., 10 or 20 μg) microinjected into the NRM markedly reduced the responses elicited by afferent C-fiber stimulation (mean 55.6%, n = 8) and the responses to noxious skin heating (mean 38.1%, n = 8), while responses to A-volleys in hind limb nerves were less attenuated (mean 73.6%, n = 8). The effects of morphine were partially or completely blocked by microinjection (10 μg) of naloxone into the NRM. It is concluded that morphine microinjection into the NRM generates descending inhibition on the transmission of nociceptive information in the dorsal horn of the spinal cord. This may partly explain the mechanisms of morphine analgesia.

Cat spinoreticular neurons: Locations, responses and changes in responses during repetitive stimulation

Neurons in the lumbosacral spinal cord which project to the medial pontomedullary reticular formation were studied in the chloralose-anesthetized cat. Such neurons, identified by antidromic activation, were found predominantly in lamina VIII and medial lamina VII, and most were found to project to the contralateral reticular formation. Receptive fields for natural stimuli were generally complex, having various combinations of excitatory and inhibitory areas ipsi- and/or contralaterally. Adequate stimuli ranged from innocuous to noxious, with the stimuli required for decreasing a neuron's activity usually more intense than the stimulus required for increasing it. Electrical stimulation of hindlimb nerves indicated the presence of extensive convergence. Responses of spinoreticular neurons were found to decline during periods of repetitive stimulation. The response decrements were found to have many of the parametric features of behavioral habituation and were similar to response decrements previously observed in the medial pontomedullary reticular formation.

Labyrinthine and somatosensory convergence upon vestibulo-ocular units.

The vestibular nuclei were investigated in 18 adult cats. Vestibulo-oculo-motor neurons were identified by antidromic stimulation of the ascending medial longitudinal fasciculus (MLF). The neurons were subjected to various stimuli: vestibular, neck, forelimb and hindlimb nerve stimulation on both sides. The recording was extracellular with micropipettes containing Fast Green. Only the medial and the superior vestibular nuclei were found to project to the MLF. All projecting units had input from the labyrinths. Excitatory response latencies to ipsilateral labyrinth stimulation never exceeded 3 msec. Both excitatory and inhibitory response latencies could be distributed into different categories. The majority of the neurons did not receive a somatosensory input, and surprisingly few convergent units could be seen. Peripheral somatosensory information apparently plays a minor role in vestibulo-ocular relations.

Ascending long spinal actions on forelimb motoneurons in the acute spinal cat.

Ascending long spinal reflex system were investigated by means of monosynaptic reflex testing in the acutely spinalized unanesthetized cat. 1. Hindlimb nerve stimulation gave bilateral facilitatory effects on the motoneuron pools of pectoralis major and physiological flexors of the forelimb such as biceps brachii, extensor carpi radialis, extensor digitorum communis, but elicited depressive effects on the physiological extensors such as triceps brachii, flexor carpi radialis, flexor digitorum profundus. 2. In the latissimus dorsi, which is the antagonist of pectoralis major, a depressive effect was elicited by the stimulation of ipsilateral hindlimb nerves, and a facilitatory effect by contralateral stimulation. 3. These effects were evoked mainly from group II afferent fibers in muscle as well as cutaneous nerves. 4. Intracellular recordings from motoneurons of extensor carpi radialis revealed EPSPs following stimulation of hindlimb nerves with time courses corresponding to those of the facilitatory effects. We failed to detect any potential changes in the motoneurons of flexor carpi radialis following stimulation of hindlimb nerves.

The action of two inhibitors of glutamic acid uptake upon amino acid-induced and synaptic excitations of thalamic neurones

Two inhibitors of glutamate uptake, glutamic acid dimethylester (GDME) and p-chloromercuriphenylsulphonate (pCMS) have been compared. When administered electrophoretically from multi-barrelled pipettes, both substances reversibly increased the actions of excitatory amino acids upon thalamic neurones, with the most pronounced effect occurring with glutamate. GDME also increased the responses evoked by threshold stimulation of hind limb nerves, while pCMS was without this action. When the kinetics of uptake of glutamate by crude suspensions of synaptosomes were examined, it appeared that GDME acts as a competitive while pCMS is a non-competitive antagonist of this process.

Functional organization of long ascending propriospinal pathways linking lumbo-sacral and cervical segments in the cat

In high spinal cats propriospinal pathways ascending from lumbo-sacral levels of the spinal cord can mediate strong excitatory and inhibitory changes in reflexes to different groups of motoneurones supplying muscles of the forelimb. Discharges evoked by electrical stimulation of hindlimb nerves could be evoked in 41% of experiments in the motoneurones of pectoralis major and minor. The latency of the discharge (8–18 msec) could be shortened by increasing the repetition frequency of the stimulus, the greatest reduction occurring in the range 1–4 Hz. Contralateral hindlimb nerves were less effective and the discharge generally occurred at a latency 1–2 msec longer than for ipsilateral nerves. Monosynaptic reflexes to pectoralis major and deep radial motoneurones supplying the physiological flexor muscles were strongly facilitated by hindlimb nerve stimulation, ipsilateral nerves being more effective than contralateral. Monosynaptic reflexes to latissimus dorsi showed a reciprocal pattern of conditioning, being depressed by ipsilateral and facilitated by contralateral hindlimb extensor nerves, the flexor nerves giving the reverse pattern. Monosynaptic reflexes to median and ulnar nerves supplying physiological extensor muscles were not significantly affected by hindlimb nerve conditioning. Polysynaptic reflexes to pectoralis major and deep radial motoneurones received initial strong facilitation followed by prolonged depression, ipsilateral hindlimb nerves being more effective than contralateral. In latissimus dorsi a reciprocal pattern similar to that for monosynaptic reflex testing was found. Polysynaptic reflexes to median and ulnar motoneurones received only prolonged depression. The hindlimb afferent nerves responsible for the discharge in forelimb motoneurones and for the facilitation and depression of forelimb reflexes include groups II and II muscle afferents and group II skin afferents, especially from quadriceps and sartorius muscles, and sural and superficial peroneal nerves, respectively. The ascending long propriospinal pathways are influenced bilaterally from hindlimb nerves and are located in the lower thoracic segments in the ventrolateral funiculus. The pathways mediate effects on ipsilateral and contralateral forelimb reflex systems, the ipsilateral projections being dominant. Part of the long ascending projection terminates monosynaptically on the motoneurones of pectoralis major. It is likely that group II afferents from ipsilateral quadriceps muscle activate the ascending tract monosynaptically and those from contralateral quadriceps disynaptically. The hypothesis is suggested that long propriospinal paths primarily represent intrinsic links between hindlimb and forelimb ‘motor centres’. The pattern of long ascending influences to groups of forelimb motoneurones corresponds closely to the sequences of hindlimb and forelimb stepping observed in normal cats. A functional role in stepping is therefore proposed for long ascending propriospinal pathways.

Spinal and medullary reflex components of the somatosympathetic reflex discharges evoked by stimulation of the group IV somatic afferents

Sympathetic reflex discharges were recorded from lumbar white rami (WR) in cats anaesthetized with chloralose. Stimulation of the group IV afferent fibres of either hindlimb nerves or adjacent spinal nerves evoked the group IV afferent reflex in CNS-intact as well as in acutely decerebrated cats. The group IV afferent reflex evoked by stimulation of hindlimb nerves in CNS-intact cats remained after decerebration, whereas it disappeared completely after spinal transection. However, in the long-kept chronic spinal cats, whose spinal cords were transected more than 8–12 weeks before experiments, this reflex reappeared. The group IV afferent reflex evoked by stimulation of adjacent spinal nerves in CNS-intact cats remained even in acute spinal cats. It could be evoked by single shock stimuli. The following conclusions are reached. (1) The group IV afferent reflex evoked by stimulation of hindlimb nerves has a central reflex pathway through the nedulla oblongata when the CNS neuraxis is intact. However, a spinal reflex pathway can also exist under special conditions such as in very long-kept chronic spinal animals. (2) The group IV afferent reflex evoked by stimulation of adjacent spinal nerves definitely has a spinal reflex pathway in CNS-intact cats.

The antagonism of the glutamate-induced and synaptic excitations of thalamic neurones

Summary Two derivatives of glutamic acid, dl -α-methylglutamate and l -glutamic acid diethylester, which themselves possess little or no excitatory action, have been found reversibly to block the excitation of thalamic neurones produced by l -glutamate. The excitatory action of dl -homocysteic acid was much less affected and that of acetylcholine unaffected by these compounds. The synaptic excitation of cells in the ventrobasal thalamus evoked by electrical stimulation of hind limb nerves was also reduced by these compounds. The results support the suggestion that glutamate may act as an excitatory synaptic transmitter in the thalamus.

Effect of fore- and hindlimb nerve stimulation on Deiter's neurones

Effect of fore- and hindlimb nerve stimulation on Deiter's neurones

Responses to a spino-olivo-cerebellar pathway in the cat.

1. Surface potentials, similar to those found by earlier workers, have been recorded from the vermis of the anterior lobe of the cerebellum following stimulation of muscular, cutaneous and articular nerves of the ipsilateral hind limb. The most conspicuous component of the response consisted of a positive potential succeeded by a smaller negative potential.2. Micro-electrode recordings showed that this component coincided both with climbing fibre responses in individual Purkinje cells, and with extracellular field potentials within the cerebellar cortex which closely resembled those found by Eccles, Llinás & Sasaki (1966) following electrical stimulation of the inferior olive.3. Stimulation of the cerebellar surface, in the region where the responses to limb nerve stimulation were largest, led to antidromic invasion of neurones of the contralateral inferior olive. The antidromic action potentials were sometimes followed by up to three orthodromic spikes. Histological techniques were used to show that these neurones were located in the caudal parts of the dorsal and medial accessory olives.4. Stimulation of nerves of the hind limb evoked discharges of the same neurones of the dorsal accessory olive which were antidromically invaded from the vermis of the anterior lobe. The nerves used (quadriceps, gastrocnemius-soleus, sural and the posterior nerve to the knee joint) were shown to excite heavily overlapping populations of neurones.5. Those neurones of the medial accessory olive, which were identified antidromically from the anterior lobe vermis, were not discharged by stimulation of hind limb nerves.6. Simultaneous recording from the surface of the anterior lobe and from the dorsal accessory olive showed that the onset of olive cell discharges occurred about 5 msec before the onset of the positive potential at the cerebellar surface.