Activity of precentral neurons during torque-triggered hand movements in awake primates.

In monkeys performing a handle-repositioning task involving primarily wrist flexion-extension (F-E) movements after a torque perturbation was delivered to the handle, single units were recorded extracellularly in the contralateral precentral cortex. Precentral neurons were identified by passive somatosensory stimulation, and were classified into five somatotopically organized populations. Based on electromyographic recordings, it was observed that flexors and extensors about the wrist joint were specifically involved in the repositioning of the handle, while many other muscles which act at the wrist and other forelimb joints were involved in the task in a supportive role. In precentral cortex, all neuronal responses observed were temporally correlated to both the sensory stimuli and the motor responses. Visual stimuli, presented simultaneously with torque perturbations, did not affect the early portion of cortical responses to such torque perturbations. In each of the five somatotopically organized neuronal populations, task-related neurons as well as task-unrelated ones were observed. A significantly larger proportion of wrist (F-E) neurons was related to the task, as compared with the other, nonwrist (F-E) populations. The above findings were discussed in the context of a hypothesis for the function of precentral cortex during voluntary limb movement in awake primates. This hypothesis incorporates a relationship between activities of populations of precentral neurons, defined with respect to their responses to peripheral events at or about single joints, and movements about the same joint.     

Excitation of dorsal and ventral respiratory group neurons by phrenic nerve afferents

The projections of phrenic nerve afferents to neurons in the dorsal (DRG) and ventral (VRG) respiratory group were studied in anesthetized, paralyzed, and vagotomized cats. Extracellular recordings of neuronal responses to vagal nerve and cervical phrenic nerve stimulation (CPNS) indicated that about one-fourth of the DRG respiratory-modulated neurons were excited by phrenic nerve afferents with an onset latency of approximately 20 ms. In addition, non-respiratory-modulated neurons within the DRG were recruited by CPNS. Although some convergence of vagal and phrenic afferent input was observed, most neurons were affected by only one type of afferent. In contrast to the DRG, only 3 out of 28 VRG respiratory-modulated neurons responded to CPNS. A second study determined that most of these neuronal responses were due to activation of diaphragmatic afferents since 90% of the DRG units activated by CPNS were also excited at a longer latency by thoracic phrenic nerve stimulation. The difference in onset latency of neuronal excitation indicates an afferent peripheral conduction velocity of about 10 m/s, which suggests that they are predominately small myelinated fibers (group III) making paucisynaptic connections with DRG neurons. Decerebration, decerebellation, and bilateral transection of the dorsal columns at C2 do not abolish the neuronal responses to cervical PNS.     

Innervation of the knee joint in the rabbit and the Formosan rock-monkey (Macaca cyclopis): a retrograde HRP study.

The number and segmental distribution of cell bodies of sensory afferents and sympathetic efferent innervating to the knee joint of the rabbit and the Formosan rock-monkey were investigated using retrograde transport with horseradish peroxidase (HRP). After injecting HRP into the articular knee joint capsule of the rabbits, labeled neurons were found in the ipsilateral L4-S2 dorsal root ganglia (DRG). However, following injection of HRP into the articular cavity of the knee joint in the rabbit and the monkey, labeled neurons were found in both the ipsilateral DRG (L5-S2 and L4-S1 of the rabbit and monkey, respectively) and in the ipsilateral sympathetic ganglia (SG) (L4-S3 (rabbit) and L3-S1 (monkey)). The majority of labeled neurons within the DRG and the SG were composed of medium and large neurons in the monkey and the rabbit, respectively. The present findings suggest that the sensory projections from and sympathetic projection to the knee joint in rabbits and monkeys are similar, but that both projections of monkeys were "shifted" one segment cranially compared to the rabbit on both projections.     

Encoding mechanisms for sensory neurons studied with a multielectrode array in the cat dorsal root ganglion

Recent advances in microelectrode array technology now permit a direct examination of the way populations of sensory neurons encode information about a limb's position in space. To address this issue, we recorded nerve impulses from about 100 single units simultaneously in the L6 and L7 dorsal root ganglia (DRG) of the anesthetized cat. Movement sensors, placed near the hip, knee, ankle, and foot, recorded passive movements of the cat's limb while it was moved pseudo-randomly. The firing rate of the neurons was correlated with the position of the limb in various coordinate systems. The firing rates were less correlated to the position of the foot in Cartesian coordinates (x, y) than in joint angular coordinates (hip, knee, ankle), or in polar coordinates. A model was developed in which position and its derivatives are encoded linearly, followed by a nonlinear spike-generating process. Adding the nonlinear portion significantly increased the correlations in all coordinate systems, and the full models were able to accurately predict the firing rates of various types of sensory neurons. The observed residual variability is captured by a simple stochastic model. Our results suggest that compact encoding models for primary afferents recorded at the DRG are well represented in polar coordinates, as has previously been suggested for the cortical and spinal representation of movement. This study illustrates how sensory receptors encode a sense of limb position, and it provides a general framework for modeling sensory encoding by populations of neurons.     

Spinal dorsal column afferent fiber composition in the pigeon: an electrophysiological investigation

Summary The spinal dorsal column of homing pigeons (Colomba livia) was investigated electrophysiologically by recording responses from individual afferent fibers at a high cervical level (segments C4-C5) to mechanical stimulation of wing skin and deep tissue. Of 157 afferent fibers 134 were cutaneous afferents. The remainder were afferents of deep receptors.Thirty of the cutaneous afferents were slowly adapting and 87 rapidly adapting (17 not identified). Rapidly adapting afferents were studied with regard to Pacinianlike characteristics (Herbst corpuscles in birds; vibration sensitive receptors). Of 43 rapidly adapting afferents 38 were classified as afferents of vibration sensitive Herbst corpuscles and 5 as non vibration sensitive rapidly adapting afferents; 44 afferents could not be studied sufficiently with regard to vibrational stimuli. The vibration sensitive Herbst corpuscle afferents had U-shaped vibrational tuning curves and responded best to vibration frequencies of 300 to 400 Hz. The 11 threshold for 300 Hz vibration ranged from 2 to 36 um. Herbst corpuscle afferents always showed strong phase coupling to the stimulus cycle.Afferents of deep receptors showed slowly adapting responses to firm pressure or movements of limbs and were classified as joint receptors. No muscle spindle afferents were encountered.Primary afferent fibers were identified in 89 cases (80 cutaneous and 9 deep), postsynaptic elements in 15 cases (11 cutaneous, 4 deep). Only slowly adapting responses were found in postsynaptic fibers.Abbreviations CV coefficient of variation - EI entrainment index - INTH interval histogram - PSTH peristimulus time histogram - RA rapidly adapting - SA slowly adapting     

Quadrupedal locomotion in squirrel monkeys (Cebidae: Saimiri sciureus): a cineradiographic study of limb kinematics and related substrate reaction forces

Quadrupedal locomotion of squirrel monkeys on small-diameter support was analyzed kinematically and kinetically to specify the timing between limb movements and substrate reaction forces. Limb kinematics was studied cineradiographically, and substrate reaction forces were synchronously recorded. Squirrel monkeys resemble most other quadrupedal primates in that they utilize a diagonal sequence/diagonal couplets gait when walking on small branches. This gait pattern and the ratio between limb length and trunk length influence limb kinematics. Proximal pivots of forelimbs and hindlimbs are on the same horizontal plane, thus giving both limbs the same functional length. However, the hindlimbs are anatomically longer than the forelimbs. Therefore, hindlimb joints must be more strongly flexed during the step cycle compared to the forelimb joints. Because the timing of ipsilateral limb movements prevents an increasing amount of forelimb retraction, the forelimb must be more protracted during the initial stance phase. At this posture, gravity acts with long moment arms at proximal forelimb joints. Squirrel monkeys support most of their weight on their hindlimbs. The timing of limb movements and substrate reaction forces shows that the shift of support to the hindlimbs is mainly done to reduce the compressive load on the forelimb. The hypothesis of the posterior weight shift as a dynamic strategy to reduce load on forelimbs, proposed by Reynolds ([1985]) Am. J. Phys. Anthropol. 67:335-349; [1985] Am. J. Phys. Anthropol. 67:351-362), is supported by the high correlation of ratios between forelimb and hindlimb peak vertical forces and the range of motion of shoulder joint and scapula in primates.     

Bilateral activation of STAT3 by phosphorylation at the tyrosine-705 (Y705) and serine-727 (S727) positions and its nuclear translocation in primary sensory neurons following unilateral sciatic nerve injury

Unilateral sciatic nerve compression (SNC) or complete sciatic nerve transection (CSNT), both varying degrees of nerve injury, induced activation of STAT3 bilaterally in the dorsal root ganglia (DRG) neurons of lumbar (L4-L5) as well as cervical (C6–C8) spinal cord segments. STAT3 activation was by phosphorylation at the tyrosine-705 (Y705) and serine-727 (S727) positions and was followed by their nuclear translocation. This is the first evidence of STAT3(S727) activation together with the well-known activation of STAT3(Y705) in primary sensory neurons upon peripheral nerve injury. Bilateral activation of STAT3 in DRG neurons of spinal segments anatomically both associated as well as non-associated with the injured nerve indicates diffusion of STAT3 activation inducers along the spinal cord. Increased levels of IL-6 protein in the CSF following nerve injury as well as activation and nuclear translocation of STAT3 in DRG after intrathecal injection of IL-6 shows that this cytokine, released into the subarachnoid space can penetrate the DRG to activate STAT3. Previous results on increased bilateral IL-6 synthesis and the present manifestation of STAT3 activation in remote DRG following unilateral sciatic nerve injury may reflect a systemic reaction of the DRG neurons to nerve injury.     

Stumbling corrective responses in healthy human subjects to rapid reversal of treadmill direction.

The kinematics of stumbling and recovery induced by a rapidly reversing treadmill is described for eight healthy adults. Stability was achieved in approximately 400 ms following treadmill reversal (initiated at heel-strike) and the ensuing stumble. It appeared to be accomplished primarily by rapid flexion of the thigh and knee of the stance limb, which prevented damage to the knee joint and lowered the trunk, and by extension of the contralateral joints (swing limb), which contacted the ground presumably to deliver an impulsive thrust to counter the backward lean of the trunk. The movements of the ankle also contributed to the recovery from the stumble, but its movements were markedly more variable among the subjects than those of the thigh and knee. The observed kinematics to some extent resembled a crossed-extension reflex, which may have been triggered by muscle, joint, cutaneous or vestibular afferents. These data should provide a baseline by which to compare groups in which recovery from stumbling is known to be deficient (e.g., the elderly).     

Convergence of forelimb afferent actions on C7-Th1 propriospinal neurones bilaterally projecting to sacral segments of the cat spinal cord

Propriospinal neurones located in the cervical enlargement and projecting bilaterally to sacral segments of the spinal cord were investigated electrophysiologically in eleven deeply anaesthetized cats. Excitatory or inhibitory postsynaptic potentials from forelimb afferents were recorded following stimulation of deep radial (DR), superficial radial (SR), median (Med) and ulnar (Uln) nerves. 26 cells were recorded from C7, 22 from C8 and 3 from Th1 segments. The majority of the cells were located in the Rexed's laminae VIII and the medial part of the lamina VII. In 10 cases no afferent input from the forelimb afferents was found. In the remaining neurones effects were evoked mostly from DR (88%) and Med (63%), less often from SR (46%) and Uln (46%). Inhibitory actions were more frequent than excitatory. The highest number of IPSPs was evoked from high threshold flexor reflex afferents (FRA)--all connections were polysynaptic. However, inhibitory actions were often evoked from group I or II muscle afferents (polysynaptic or disynaptic) and, less frequently, from cutaneous afferents (mostly polysynaptic). Di- or polysynaptic IPSPs often accompanied monosynaptic EPSPs from group I or II muscle afferents. Disynaptic or polysynaptic EPSPs from muscle and cutaneous afferents were also recorded in many neurones, while polysynaptic EPSPs from FRA were observed only exceptionally. Various patterns of convergence in individual neuronal subpopulations indicate that they integrate different types of the afferent input from various muscle and cutaneous receptors of the distal forelimb. They transmit this information to motor centers controlling hind limb muscles, forming a part of the system contributing to the process of coordination of movements of fore--and hind--limbs.     

Sustained neurochemical plasticity in central terminals of mouse DRG neurons following colitis

Sensitization of dorsal root ganglia (DRG) neurons is an important mechanism underlying the expression of chronic abdominal pain caused by intestinal inflammation. Most studies have focused on changes in the peripheral terminals of DRG neurons in the inflamed intestine but recent evidence suggests that the sprouting of central nerve terminals in the dorsal horn is also important. Therefore, we examine the time course and reversibility of changes in the distribution of immunoreactivity for substance P (SP), a marker of the central terminals of DRG neurons, in the spinal cord during and following dextran sulphate sodium (DSS)-induced colitis in mice. Acute and chronic treatment with DSS significantly increased SP immunoreactivity in thoracic and lumbosacral spinal cord segments. This increase developed over several weeks and was evident in both the superficial laminae of the dorsal horn and in lamina X. These increases persisted for 5 weeks following cessation of both the acute and chronic models. The increase in SP immunoreactivity was not observed in segments of the cervical spinal cord, which were not innervated by the axons of colonic afferent neurons. DRG neurons dissociated following acute DSS-colitis exhibited increased neurite sprouting compared with neurons dissociated from control mice. These data suggest significant colitis-induced enhancements in neuropeptide expression in DRG neuron central terminals. Such neurotransmitter plasticity persists beyond the period of active inflammation and might contribute to a sustained increase in nociceptive signaling following the resolution of inflammation.     

Response properties of thick myelinated group II afferents in the medial articular nerve of normal and inflamed knee joints of the cat.

This study investigated the responses to innocuous and noxious mechanical stimuli of joint mechanoreceptors with thick myelinated articular afferents (conduction velocities 21-65 m/sec) in the medial articular nerve of the cat's knee. In nine experiments, we examined whether acute arthritis would modify the discharge properties. The vast majority of the group II afferents were excited by gentle local stimuli and by movements in the working range of the knee. Although they encoded pressure and particular movement stimuli up to the noxious range, their responses were more closely related to the particular type of stimulus (e.g., a movement in a specific direction) than to its intensity (innocuous vs. noxious). In inflamed joints, the response patterns of group II units were similar with regard to local mechanical thresholds, thresholds for passive movements, and patterns of responses to passive movements. In both situations, most units had no resting activity. These results suggest that articular group II afferents do not play a significant role in nociception. Rather, they subserve proprioceptive functions such as deep pressure sensation and kinesthesia in normal as well as inflamed joints.     

Development of "normal" dermatomes and somatotopic maps by "abnormal" populations of cutaneous neurons

During development, motor and sensory axons grow to peripheral targets with remarkable precision. Whereas much has been learned about the development of motoneuron connectivity, less is known about the regulation of cutaneous innervation. In adults, dorsal root ganglia (DRG) innervate characteristic skin regions, termed dermatomes, and their axons project somatotopically in the dorsal horn. Here, we have investigated whether cutaneous neurons are selectively matched with specific skin regions, and whether peripheral target skin influences the central connections of cutaneous neurons. To address these questions, we shifted limb buds rostrally in chick embryos prior to axon outgrowth, causing DRGs to innervate novel skin regions, and mapped the resulting dermatomes and central projections. Following limb shifts, cutaneous innervation arose from more rostral and from fewer DRGs than normal, but the overall dermatome pattern was preserved. Thus, DRGs parcel out innervation of skin in a consistent manner, with no indication of matching between skin and DRGs. Similarly, cutaneous nerves established a "normal" somatotopic map in the dorsal horn, but in more rostral segments than usual. Thus, the peripheral target skin may influence the pattern of CNS projections, but does not direct cutaneous axons to specific populations of neurons in the dorsal horn.     

Responses of celiac and cervical vagal afferents to infusions of lipids in the jejunum or ileum of the rat

Multiunit celiac and single-unit cervical recordings of vagal afferents were performed before and during infusions of fatty acids, triglycerides, or saline into either the ileum or jejunum of the rat. In multiunit recordings, lipids increased activity of vagal afferents to a greater extent than saline. The greatest increases in vagal afferent activity resulted from infusions of linoleic acid, conjugated linoleic acid, or oleic acid. The triglycerides, corn oil or Intralipid, were less effective than the fatty acids in affecting vagal afferent activity. Ileal pretreatment with the hydrophobic surfactant Pluronic L-81 significantly attenuated the response of celiac vagal afferents to ileal infusion of linoleic acid. Single-unit recordings of cervical vagal afferents supported the multiunit data in showing lipid-induced increased vagal afferent activity in approximately 50% of ileal units sampled and 100% of a limited number of jejunal units sampled. These data demonstrate that free fatty acids can activate ileal and jejunal vagal afferents in the rat, and this effect can be attenuated by pretreatment with a chylomicron inhibitor. These data are consistent with the view that lipid-induced activation of vagal afferents could be a potential substrate for the inhibitory effects of intestinal lipids on gastrointestinal function, food intake, and body weight gain.     

Shoulder movements during quadrupedal locomotion in arboreal primates

The kinematics of scapula and shoulder joint movements were analyzed in three species of arboreal quadrupedal primates using cineradiography. Our findings indicate that scapular movement is highly important for forelimb movement in primates with this ancestral mode of locomotion. Retroversion of the scapula (syn. caudal rotation or extension) during the stance phase contributes more than 40% to the stride length of the forelimb. Lateral forelimb excursions, a general feature for arboreal primates, are based on complex three-dimensional scapular movements guided by the clavicle. Humeral abduction is achieved by scapular abduction and transversal rotation of the scapula about its longitudinal axis, and is therefore strikingly different from humeral abduction in humans. At the same time, the movements of the shoulder joint are limited to flexion and extension only.     

AMPA and NMDA glutamate receptors are found in both peptidergic and non-peptidergic primary afferent neurons in the rat

Two distinct classes of nociceptive primary afferents, peptidergic and non-peptidergic, respond similarly to acute noxious stimulation; however the peptidergic afferents are more likely to play a role in inflammatory pain, while the non-peptidergic afferents may be more characteristically involved in neuropathic pain. Using multiple immunofluorescence, we determined the proportions of neurons in the rat L4 dorsal root ganglion (DRG) that co-express AMPA or NMDA glutamate receptors and markers for the peptidergic and non-peptidergic classes of primary afferents, substance P and P2X(3), respectively. The fraction of DRG neurons immunostained for the NR1 subunit of the NMDA receptor (40%) was significantly higher than that of DRG neurons immunostained for the GluR2/3 (27%) or the GluR4 (34%) subunits of the AMPA receptor. Of all DRG neurons double-immunostained for glutamate receptor subunits and either marker for peptidergic and non-peptidergic afferents, a significantly larger proportion expressed GluR4 than GluR2/3 or NR1 and in a significantly larger proportion of P2X(3)- than SP-positive DRG neurons. These observations support the idea that nociceptors, involved primarily in the mediation of neuropathic pain, may be presynaptically modulated by GluR4-containing AMPA receptors.     

Somatosensory activity relevant for motor output. A summary of presentations and discussion

Several aspects of the function of receptors which contribute to somatic sensations are reviewed. First, there is evidence for a role of large-diameter cutaneous afferents in the reflex regulation of precision movements by the hand. Second, large-diameter muscle afferents from the intrinsic muscles of the hand, probably from primary muscle spindle afferents, can evoke specific sensations of finger movement. Third, the variable relationship between discharges in human C fibers from the hand and the specific sensation of pain is investigated. Activity in large-diameter cutaneous afferents can probably modify this sensation. Finally, the properties of small-diameter afferent fibers innervating joints are shown to be consistent with a role in the reflex regulation of joint integrity.     

An equilibrium-point model of electromyographic patterns during single-joint movements based on experimentally reconstructed control signals

The purpose of this work has been to develop a model of electromyographic (EMG) patterns during single-joint movements based on a version of the equilibrium-point hypothesis, a method for experimental reconstruction of the joint compliant characteristics, the dual-strategy hypothesis, and a kinematic model of movement trajectory. EMG patterns are considered emergent properties of hypothetical control patterns that are equally affected by the control signals and peripheral feedback reflecting actual movement trajectory. A computer model generated the EMG patterns based on simulated movement kinematics and hypothetical control signals derived from the reconstructed joint compliant characteristics. The model predictions have been compared to published recordings of movement kinematics and EMG patterns in a variety of movement conditions, including movements over different distances, at different speeds, against different-known inertial loads, and in conditions of possible unexpected decrease in the inertial load. Changes in task parameters within the model led to simulated EMG patterns qualitatively similar to the experimentally recorded EMG patterns. The model's predictive power compares it favourably to the existing models of the EMG patterns.     

Response of Cat Cortical Neurons to Position and Movement of the Femur

The contribution of joint afferents to the response of cortical neurons in area 3a to mechanical stimulation of the contralateral hindlimb was evaluated in cats anesthetized with sodium pentobarbital and paralyzed with pancuronium bromide. The hindlimb projection to the pericruciate cortex was established by recording the evoked potentials to electrical stimulation of the sciatic nerve and some of its branches, the biceps-semitendinosus and the quadratus femoris

Out of 169 neurons, 63 responded exclusively to cutaneous stimuli (superficial), whereas the others could be activated by local pressure of hindlimb muscles and/or by joint rotation (deep). Deep neurons were classified as slowly adapting (SA) or rapidly adapting (RA) units. In the neurons responding exclusively to joint rotation, the site of the receptive field could not be identified with certainty. In 13 deep neurons, their firing was affected by rotation of multiple joints of the contralateral hindlimb

In an attempt to identify the source of activation of cortical neurons, partial denervations and muscle disconnections were performed in five animals to isolate and stimulate the hip capsule. In these preparations, in 14 of 15 cortical neurons the source of activation was localized in the periarticular muscles, with no response to mechanical stimulation of the joint capsule. Only one neuron (S A) could be selectively excited by punctate pressure on the hip capsule

Our results suggest that in neurons of area 3a of the cat, the information about the position of the femur relies mainly on muscle afferents     

Peripheral specification of Ia synaptic input to motoneurons innervating foreign target muscles

Muscle sensory neurons, called Ia afferents, make monosynaptic connections with functionally related sets of motoneurons in the spinal cord. Previous work has suggested that peripheral target muscles play a major role in determining the central connections of Ia afferents with motoneurons. Here, we ask whether motoneurons can also be influenced by their target muscles in terms of the monosynaptic input they receive from Ia afferents, by transplanting thoracic motoneurons into the lumbosacral spinal cord so that they innervate foreign muscles. Three or four segments of thoracic neural tube from stage 14-15 chicken embryos were transplanted to the lumbosacral region of stage 16-17 embryos, and electrophysiological recordings were made from transplanted motoneurons after the embryos had reached stage 38-40. Transplanted thoracic motoneurons innervated limb muscles and received monosynaptic inputs from Ia afferents. These connections were not random: Most of the connections were formed between Ia afferents and motoneurons projecting to the same muscle (homonymous connections). Few aberrant connections were found although the anatomical distribution of afferents in the transplant indicated that they had ample opportunity to contact inappropriate motoneurons. We conclude that although peripheral target cues are not sufficient to respecify an already committed motoneuron (turn a thoracic motoneuron into a lumbosacral motoneuron), they do provide sufficient information for Ia afferent input to be functionally correct.