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We tested the hypothesis that the cognitive impairment associated with inflammatory pain may result from dysregulation of the top-down control of locus ceruleus's (LC) activity by the medial prefrontal cortex (mPFC). Injection of complete Freund's adjuvant (CFA) served as a model for inflammatory pain. The CFA injection decreased the thermal thresholds in both sexes but only the male mice showed increased anxiety-like behavior and diminished cognition, while the females were not affected. Increased calcium fluorescence, a marker for neuronal activity, was detected by photometry in the mPFC of males but not in females with CFA. Next, while chemogenetic inhibition of the projections from the mPFC to the LC improved the object recognition memory of males with pain, the inhibition of the mPFC to LC pathway in female mice produced anxiolysis and spatial memory deficits. The behavior results prompted us to compare the reciprocal innervation of mPFC and LC between the sexes. We used an anterograde transsynaptic tagging technique, which relies on postsynaptic cre transfer, to assess the innervation of LC by mPFC efferents. The males showed a higher rate of postsynaptic cre transfer into LC neurons from mPFC efferents than the females. And vice versa, a retrograde tracing experiment demonstrated that LC to mPFC projection neurons were more numerous in females when compared to males. In conclusion, we provide evidence that subtle differences in the reciprocal neuronal circuit between the LC and mPFC may contribute to sex differences associated with the adverse cognitive effects of inflammatory pain.

As a strategy to address the difficulties encountered when modeling and controlling a musculoskeletal system, we present a straightforward implementation of an autonomous decentralized motion control system in this paper; the system is inspired by the spinal reflex system of animals. We developed an artificial receptor, a muscle, and a neuron to mechanically implement the reflex mechanisms of animals. Among the reflex mechanisms, this paper presents a reflex system with reciprocal innervation for a musculoskeletal quasi-quadruped robot, including antagonist muscles. In the experiments, the robot autonomously generated a leg trajectory and a gait pattern with smooth alternating motions of the antagonist muscles through the interaction between the body, the ground, and the artificial reflex systems. To evaluate the reciprocal innervation, we compared the developed robot with one that does not include antagonist muscles. The reciprocal innervation allows for twice as many muscle implementations as those offered by the robot without antagonist muscles. Moreover, it improves the running speed by 5% on average and the flexion and extension velocities of all joints by 28% on average at around touchdowns and liftoffs of the foot. This successful result lead to implement more advanced nervous systems by solely mechanical devices.

The body structure of an anatomically correct tendon-driven musculoskeletal humanoid is complex, and the difference between its geometric model and the actual robot is very large because expressing the complex routes of tendon wires in a geometric model is very difficult. If we move a tendon-driven musculoskeletal humanoid by the tendon wire lengths of the geometric model, unintended muscle tension and slack will emerge. In some cases, this can lead to the wreckage of the actual robot. To solve this problem, we focused on reciprocal innervation in the human nervous system, and then implemented antagonist inhibition control (AIC)-based on the reflex. This control makes it possible to avoid unnecessary internal muscle tension and slack of tendon wires caused by model error, and to perform wide range motion safely for a long time. To verify its effectiveness, we applied AIC to the upper limb of the tendon-driven musculoskeletal humanoid, Kengoro, and succeeded in dangling for 14 min and doing pull-ups.

Sensory and motor innervation of the proboscis by branches of the maxillary and labial nerves of the worker honey bee has been investigated in specimens stained vitally by methylene blue or viewed by scanning electron microscopy. A chordotonal organ consisting of a single scolopidium is present in the maxillary palp. Flexion of the maxillary palp occurs only passively, induced by the flexion of the galea. This chordotonal organ may function as a proprioceptor for the movement of the galea. Another chordotonal organ exists in the prementum of the labium. It contains, on the average, 12 sensory cells and presumably responds to the bending of the labial palp. A nerve-net of bipolar cells arises from the sensory branches of the maxillary nerve. Free nerve endings derived from the periphery of this nerve-net expand broadly on the intersegmental membranes connected to the stipes. The right and left nerves to the dilator muscles of the salivarium exchange branches, resulting in the reciprocal innervation of each muscle.

We present a model for the autonomous learning of active binocular vision using a recently developed biome-chanical model of the human oculomotor system. The model is formulated in the Active Efficient Coding (AEC) framework, a recent generalization of classic efficient coding theories to active perception. The model simultaneously learns how to efficiently encode binocular images and how to generate accurate vergence eye movements that facilitate efficient encoding of the visual input. In order to resolve the redundancy problem arising from the actuation of the eyes through antagonistic muscle pairs, we consider the metabolic costs associated with eye movements. We show that the model successfully learns to trade off vergence accuracy against the associated metabolic costs, producing high fidelity vergence eye movements obeying Sherrington’s law of reciprocal innervation.

Human studies in the past three decades have provided us with an emerging understanding of how cortical and spinal networks collaborate to ensure the vast repertoire of human behaviors. Humans have direct cortical connections to spinal motoneurons, which bypass spinal interneurons and exert a direct (willful) muscle control with the aid of a context-dependent integration of somatosensory and visual information at cortical level. However, spinal networks also play an important role. Sensory feedback through spinal circuitries is integrated with central motor commands and contributes importantly to the muscle activity underlying voluntary movements. Regulation of spinal interneurons is used to switch between motor states such as locomotion (reciprocal innervation) and stance (coactivation pattern). Cortical regulation of presynaptic inhibition of sensory afferents may focus the central motor command by opening or closing sensory feedback pathways. In the future, human studies of spinal motor control, in close collaboration with animal studies on the molecular biology of the spinal cord, will continue to document the neural basis for human behavior.

It is worth noting that while early anatomists like Ramon y Cajal, and later Lorente de No, described many of the cell types of the cerebral cortex, and they knew of Sherrington's evidence for active inhibition, they made no attempt to differentiate inhibitory from excitatory cells. That step only came much later when the fundamental details of the underlying biophysics and ionic basis of inhibitory synapses were worked out by Eccles and his colleagues and their functional data were correlated with the morphology and ultrastructure of the synapses of the neurons.For Sherrington, excitatory and inhibitory neurons were always hand-in-glove and together they provided the algebra of the nervous system: “The net change which results there when the two areas are stimulated concurrently is an algebraic sum of the plus and minus effects producible separately by stimulating singly the two antagonistic nerves” [18xOn the reciprocal innervation of antagonistic muscles. Thirteenth note. On the antagonism between reflex inhibition and reflex excitation. Sherrington, C. Proc. R. Soc. Lond. B. 1908; 80: 565–578CrossrefSee all References[18]. In recurrent circuits, there is an inherent balance between excitation and inhibition and because these recurrent excitatory circuits offer the means of amplification, small changes in the timing or strength of inhibition can effectively change the response of the entire network.We have emphasised the importance of the spike threshold, because neurons that are below threshold no longer contribute to the network activity. By keeping the membrane potential below threshold, inhibitory neurons can control dynamically the configuration of the circuit. While past research has focused almost exclusively on the output of the inhibitory neurons, one crucial aspect of future circuit analysis is to determine the source of the inputs to the inhibitory neurons and to then combine this with knowledge of the dynamics of spiking patterns and synaptic plasticity.

Eyelid movements are mediated mainly by the orbicularis oculi and the levator palpebrae superioris muscles. In blinking they show a strictly reciprocal innervation. Blepharospasm manifests as involuntary eyelid closure, however, there are also a number other diseases resulting in the inability to open the eyelid. We analysed clinical and electromyographical findings in 81 patients with disturbances of eyelid opening. Among these were 63 with tonic or clonic dystonic activity only in the orbicular part of orbicularis oculi muscle, 43 with additional dystonic activity in the palpebral part of orbicularis oculi muscle = idiopathic blepharospasm. Ten showed isolated activity in the palpebral part of orbicularis oculi muscle = palpebral variant of blepharospasm. Four exhibited synchronous activity in the orbicularis oculi and the levator palpebrae superioris muscles = disturbance of the antagonistic inhibition. Another four had no activity in the levator palpebrae superioris muscle while activity in the palpebral part of orbicularis oculi muscle was normal = apraxia of eyelid opening. A distinction is relevant for the therapeutic modality and the exact spot as which to inject botulinum toxin. In apraxia of eyelid opening after manual opening the eyelid remains open up to the next contraction of the orbicularis oculi muscle (Zwickau's eye sign).

Pseudo-inverse kinematics, under which small movements are produced by the least possible sum square changes in motor command, has been proposed as a unifying principle for the elimination of redundancy in general biological motor control systems (Pellionisz 1984) and in particular in the oculomotor system (Daunicht 1988, 1991). We have noted elsewhere (Dean et al. 1999) that this principle is incomplete without first specifying a parameterisation of motor command space and we proposed that the relevant motor command parameter is summed motor unit firing rate. Under this assumption we were able to show that pseudo-inverse control of the horizontal extraocular muscles is consistent with available motor pool firing rate data. In this paper we extend this result to three dimensions and all six extraocular muscles, showing that pseudo-inverse control is consistent with published firing rate data for a realistic model of oculomotor kinematics. We suggest that pseudo-inverse control may represent a common currency for modular control of many degree of freedom systems while its implementation may be a consequence of the minimisation of a more ecologically relevant parameter such as post-saccadic retinal slip.

Background: Treatment procedures for injuries of the flexor and extensor tendons have not been principally altered by the introduction of refined surgical techniques, new suture material, or the results of functional post-treatment. However, the treatment procedures have been more accurately defined and are now performed with greater precision. Methods: The concept of decompressing the suture, as described by Kleinert, is based on the principle of reciprocal innervation of agonists and antagonists. Pressure on the suture site is reduced by external dynamic spring splints. Results: Thus, the favourable results of functional post-treatment for injuries of the flexor tendon could be applied to extensor tendon injuries in zones IV–VIII as well. Three hundred and fifty patients have been treated by this suture technique and a dynamic splint, and were then followed. With the exception of three re-ruptures in the first ray, very good or good results were achieved. However, injuries in zones I–III are still mainly treated by static procedures. Three hundred and four flexor tendon injuries were treated with a primary flexor tendon suture. Seven per cent of our patients achieved a very good or good result, 3 % a satisfactory result. The re-rupture rate was less than 0.7 %, being below the rates reported in the published literature. Conclusions: A dynamic cast following surgery for recent extensor and flexor tendon injuries, in conjunction with an exact surgical technique, are essential for a smooth, early and good functional outcome of the treatment. The cast must provide complete decompression of the sutured tendon.

Reciprocal synapses are characterized by the presence of both afferent and efferent types of synaptic specializations between two cells. They have been described at the neural poles of outer hair cells (OHCs) in humans with advanced age and two monkey species. Our objective was to study the innervation of the OHCs and determine if reciprocal synapses were present in a young (8-month-old infant) human subject. We studied the synaptic and cytoplasmic morphology of 162 nerve terminals innervating 29 OHCs using serial section transmission electron microscopy. Seventy-six percent of all OHCs were innervated by terminals with reciprocal synapses. This prevalence increased from the first toward the third row (p < 0.001), and 100% of OHCs in the third row demonstrated at least one reciprocal synapse. The prevalence of terminals with reciprocal synapses was higher in the human infant than in older human subjects and was very similar to what has been reported for the chimpanzee. Reciprocal synapses occur in sufficient numbers to be physiologically significant in primates. The nerve terminals were found to segregate into two groups on the basis of their cytoplasmic morphological characteristics: (1) vesicle-rich/neurofilament-poor (VR/NP) and (2) vesicle-poor/neurofilament-rich (VP/NR). All afferent and reciprocal terminals were of the VP/NR variety. The majority of the efferent terminals originated from VR/NP nerve fibers (classical olivocochlear morphology), but 23.5% of the efferent terminals were VP/NR. The hypothesis that peripheral processes of type II spiral ganglion cells form classical afferent, reciprocal, and a number of purely presynaptic terminals on OHCs is discussed. The presence of different types of synaptic specializations on OHCs formed by nerve fibers of the same type (VP/NR) suggests the existence of reciprocal neuronal circuits between OHCs sharing the dendritic arborization of a type II spiral ganglion cell.

A patient with adult-onset Still’s disease (AOSD) developed periodic horizontal micro-saccadic oscillations and periodic rapid clockwise torsional eye movements followed by counterclockwise torsional drifts (see video). Neuroimaging studies were normal. Tests for paraneoplastic antibodies were negative. Details of the clinical presentation and experimental methods are presented in supplementary material 1. Horizontal saccades were faster than normal (supplementary material 2). There were bursts of horizontal saccadic oscillations without intersaccadic intervals (21.6 ± 0.4 Hz) and clockwise rapid torsional eye movement (top pole rotating towards the right ear) that had the same peak velocity-amplitude relationship as torsional quick phases of nystagmus (Fig. 1). These rapid torsional movements were followed by a drift (0.8 ± 0.2 deg/s) that brought the eyes to baseline. Low-frequency vertical and torsional oscillations were also seen (median: 3.4 and 3.1 Hz, respectively; Fig. 1b, d). The onset of rapid torsion and the horizontal saccadic oscillations were not always related (i.e., torsion did not trigger the horizontal oscillations or vice versa) (Fig. 2a). The median frequency of the pathological, spontaneous, horizontal saccadic oscillations during fixation (26.3 Hz) was not significantly different from the frequency of the physiological horizontal saccadic oscillations that are seen during orthogonal (vertical) saccades (21.9 Hz) (One-way ANOVA: p = 0.2) [6]. The median peak velocity of the pathological horizontal saccadic oscillations (14.8 deg/s) was significantly less than that of the corresponding horizontal saccadic oscillations during orthogonal (vertical) saccades (37.8 deg/s: One-way ANOVA: p 0.001; Fig. 2c). The median frequencies of the vertical (3.4 Hz) and torsional (3.1 Hz) pathological oscillations were lower than the corresponding frequencies of torsional (22.9 Hz) or vertical (21.6 Hz) oscillations during orthogonal (horizontal) saccades (One-way ANOVA: p 0.001; not shown in figure). A hypothesis to explain the pathophysiology of periodic saccadic oscillations in our patient is that saccadic burst neurons, excitatory burst neurons (EBN) and inhibitory burst neurons (IBN), comprise a reciprocally innervated premotor circuit. Their membranes contain ion channels that are important for the rebound increase in neural firing after transient external inhibition—post-inhibitory rebound (PIR) [4, 9]. Such reciprocal innervation and PIR make this neural circuit prone to oscillate [2, 3, 5–7]. We speculate that in our patient an immune mediated abnormal increase in the excitability of the burst neurons (either by reducing inhibition or increasing excitation) led to the bursts of pathological microsaccadic oscillations. Since the pattern of oculomotor dysfunction in our patient is not seen in all AOSD patients, just the presence of an immune mediated effect on burst neurons may not be sufficient to increase their excitability enough to cause oscillations. The patient might also need the appropriate genetic background (i.e., a Electronic supplementary material The online version of this article (doi:10.1007/s00415-009-5308-y) contains supplementary material, which is available to authorized users.

The connections of a potential auditory circuit were determined in the medulla of the toadfish (Opsanus tau). Fluorescent dextran amines placed in the medial torus semicircularis (mTS) retrogradely filled cells primarily in the dorsal region of the descending octaval nuclei (DON) with contralateral predominance. Fluorescent dextran amines placed in the DON revealed commissural fibers that cross the midline with the internal arcuate tract. The interconnections are consistent with a dorsal-ventral organization of the DON: reciprocal innervation is present for the left and right dorsal zones of the DON and for the left and right ventral zones of the DON. Based on projections to the medial (auditory) TS and the reciprocal connections, the dorsal region of the DON appears to be the major auditory processing site in the medulla and also may be a site for directional, binaural comparisons. The ventral region of the DON may be a site for bilateral vestibular processing. Double-labelling experiments revealed that some of the descending octaval cells projecting to the contralateral DON also project to the mTS. Based on the auditory pathway indicated by this study, future neurophysiological investigations of sensitivity to directional sound stimuli should begin in the dorsal DON of the toadfish.

Summary This study investigated the influence on pelvic mobility in children with cerebral palsy of a mechanical saddle (BABS) with imitates the movement of a horse at walk. Using a matched pairs design, subjects were selected and matched into 13 pairs. Subjects sat on either the BABS or a static saddle ten times for ten minutes over four weeks. Passive pelvic movement was measured from photographs taken at end range of passive anterior and then posterior pelvic tilt, before and after the trial. Using a related t-test a significant increase in passive pelvic antero-posterior tilt was found with subjects who used the BABS. The astride position may have influenced pelvic movement as some of the subjects on the static saddle showed an increase in range; but the significant difference between the two groups was attributed to the BABS movement. Facilitation of more normal postural tone, more appropriate reciprocal innervation and possible increased soft tissue extensibility are likely to have facilitated the increase in passive pelvic movement. These results indicate that the movement of a horse at walk can facilitate pelvic movement; the BABS and conventional horse riding are valuable tools in the physiotherapy treatment of children with cerebral palsy.

Kisspeptin (KP) neurones in the rostral periventricular area of the third ventricle (RP3V) and arcuate nucleus (Arc) are important elements in the neuronal circuitry regulating gonadotropin-releasing hormone (GnRH) secretion. KP and co-synthesised neuropeptides/neurotransmitters act directly on GnRH perikarya and processes. GnRH neurones not only form the final output pathway regulating the reproductive functions of the anterior pituitary gland, but also provide neuronal input to sites within the hypothalamus. The current double-label immunohistochemical studies investigated whether GnRH-immunoreactive (IR) projections to the RP3V and/or Arc establish morphological connections with KP-IR neurones at these sites. To optimise visualisation of KP immunoreactivity in, respectively, the RP3V and Arc, ovariectomised (OVX) oestrogen-treated and OVX oil-treated female mice were studied. Confocal laser microscopic analysis of immunofluorescent specimens revealed GnRH-IR axon varicosities in apposition to approximately 25% of the KP-IR neurones in the RP3V and 50% of the KP-IR neurones in the Arc. At the ultrastructural level, GnRH-IR neurones were seen to establish asymmetric synaptic contacts, which usually reflect excitatory neurotransmission, with KP-IR neurones in both the RP3V and Arc. Together with previous data, these findings indicate reciprocal connectivity between both of the KP cell populations and the GnRH neuronal system. The functional significance of the GnRH-IR input to the two separate KP cell populations requires electrophysiological investigation.

This research examined the correlation between peroneal nerve stimulation and the response of voluntarily recruited rhythmically firing soleus motor units (MUs). Two hundred and twenty-five MUs were recorded in 10 neurologically normal adult subjects, eight men and two women (mean age 32.3 yr). The investigation complemented previous research by re-examining reciprocal innervation patterns while controlling for the effects of two levels of stimulation (0.9 and 1.25 motor threshold) and two ankle positions (15 degrees and 45 degrees of plantarflexion). Motor unit responses were assessed by peristimulus time histogram (PSTH) analysis and a cumulative sum (CUSUM) procedure. The responses were grouped into five categories according to latency values and the sign of the firing rate response. Results demonstrated stimulus intensity effects for all categories except the short latency (28-48 ms) facilitatory response category (P < 0.05). No effects attributed solely to ankle position were demonstrated. Cutaneous afferents were not found to contribute to the response at the lower stimulus intensity, but significant effects were observed at 1.25 motor threshold. Latency values indicate that reciprocal inhibition, reciprocal excitation, and/or heteronymous excitation occur at the spinal cord level. The concept of reciprocal excitation is questioned. Possible physiological mechanisms associated with short latency excitations and inhibitions are discussed.

The aim of this work was to evaluate the short-term reeducative efficacy by an isokinetic flexion-extension test of the knee in male patients affected by neurological problems/diseases because of vascular infarct. Fifty males, average age 52.5 years, all affected by left normotonic hemiparesis, have been studied by a computerized isokinetic flexion-extension test of the knee at 60 degrees/s and endurance at 180 degrees/s O-min duration). They were all examined before and after the standardized rehabilitative treatment of 4 years. Each test was performed first on the healthy side and then on the paretic side; the control group was composed of 20 healthy people of the same age. The parameters examined in the test at 60 degrees/s were the following: time to reach peak torque; time to reach isokinesis; time of extensor/flexor transition and vice versa (reciprocal innervation). The parameters evaluated in the endurance test were: peak torque; total work performed and the number of repetitions required to cause a 20, 30 and 50% decrease in the total work slope, the gradient of the fitted line. The results show that, after treatment, muscle strength of the paretic side increased significantly, but it approximates half of the healthy limb values; the difficulties, while of alternate (reciprocal) recruitment in the hemiplegic patient, still remain. In the endurance test the healthy side has functional values between the normal values and those of the pathological side.

Neurons may serve different functions over the course of an organism’s life. Recent evidence suggests that cortical subplate neurons including those that reside in the white matter may perform longitudinal multi-tasking at different stages of development. These cells play a key role in early cortical development in coordinating thalamocortical reciprocal innervation. At later stages of development, they become integrated within the cortical microcircuitry. This type of longitudinal multi-tasking can enhance the capacity for information processing by populations of cells serving different functions over the lifespan. Subplate cells are initially derived when cells from the ventricular zone underlying the cortex migrate to the cortical preplate that is subsequently split by the differentiating neurons of the cortical plate with some neurons locating in the marginal zone and others settling below in the subplate (SP). While the cortical plate neurons form most of the cortical layers (layers 2-6), the marginal zone neurons form layer 1 and the SP neurons become interstitial cells of the white matter as well as forming a compact sublayer along the bottom of layer 6. After serving as transient innervation targets for thalamocortical axons, most of these cells die and layer 4 neurons become innervated by thalamic axons. However, 10-20% survives, remaining into adulthood along the bottom of layer 6 and as a scattered population of interstitial neurons in the white matter. Surviving subplate cells’ axons project throughout the overlying laminae, reaching layer 1 and issuing axon collaterals within white matter and in lower layer 6. This suggests that they participate in local synaptic networks, as well. Moreover, they receive excitatory and inhibitory synaptic inputs, potentially monitoring outputs from axon collaterals of cortical efferents, from cortical afferents and/or from each other. We explore our understanding of the functional connectivity of these cells at different stages of development.

The design, development and construction of an electronic active model (EAM) were proposed. The model was based on the reciprocal innervation mechanical model for horizontal eye movements and was intended to emulate the biodynamic rotatory properties of a human eye plant caused by neurologic activation signals on the lateral and medial extraocular muscles. Biodynamic properties of the mechanical eye plant, such as viscosity, inertia and elasticity, were included in the EAM in order to obtain a similar response. Apart from these features, voltage controlled resistors (VCRs) based on MOSFET to keep the nonlinearity of the plant were also included. These active elements, together with passive components, constitute the structure of the extraocular muscles, eyeball and tissues around the eyeball. The activation of agonist-antagonist signals were generated by two voltage controlled sources to reproduce the neurological activity. In this way, applying the appropriate signals to generate saccadic movements was obtained by a voltage signal proportional to the velocity of the eye torque. This signal allows one to obtain information relating to acceleration and position in order to validate the EAM. Due to this capability to emulate saccadic movements, the EAM makes it possible to reproduce involuntary eye movements caused by pathologies such as Horizontal Nystagmus. Finally, some of the EAM’s advantages lie in its response velocity and the ease of obtaining continuous records for the dynamic eyeball response in a signal that features ease of recording and application in biomedical areas, and is particularly relevant to specialists such as Neuro-ophthalmologists, ophthalmologists and optometrist, and even for medical education.

Based on the mechanical model of reciprocal innervation of horizontal eye movements, we propose the design, development and construction of an active-electro model (AEM) to emulate the biodynamics of the human eye from neurological activation in the lateral and medial extraocular muscles. The AEM design characteristics provide mechanical properties such as viscosity, inertia and elasticity of the ocular plant. The model includes together with these features a voltage-controlled resistor (VCR), to maintain the nonlinearity of the plant. These active elements together with passive components form the structure of the extraocular muscles, eyeball and surrounding tissues in the orbital cavity. Characteristics of agonist-antagonist activation is generated by two controlled voltage sources in order to adequately reproduce the neurological activity that generates saccadic movements and thus produces a voltage signal proportional to the speed of the eye. This signal can also provide information about the acceleration and position in order to validate the AEM. Because of this feature to emulate saccadic movements, the AEM is able to reproduce the involuntary eye movements caused by conditions such as horizontal nystagmus. Finally, some advantages of AEM are in the rapid response and ease of obtaining the records of the dynamics of the eyeball movement in evoked responses and applicability to biomedical fields as well as neuroophthalmologists, ophthalmologists and optometrists.

Based on reciprocal innervation mechanical model for horizontal eye movements, was proposed the design, development and construction of an electronic active model (EAM) to emulate the biodynamics rotatory properties of a human eye plant caused by neurologic activation signals on lateral and medial extraocular muscles. Biodynamic properties as viscosity, inertia and elasticity of the mechanical eye plant were included into the electrical network to obtain a similar response. Apart from these features, were include voltage controlled resistors (VCRs) based on MOSFET to keep the nonlinear of the plant. These active elements altogether with passive components constitute the structure of extraocular muscles, eye ball and tissues around the eye ball. Activation agonist-antagonist signals were generated by two voltage controlled sources to reproduce the neurological activity. In this way, applying the appropriate signals to generate saccadic movements, was obtained a voltage signal proportional to velocity of the eye torque. This signal allows obtain information of acceleration and position in order to validate the EAM. Finally, some of the EAM advantages lie on its response velocity and ease to obtain continues records of the dynamic eyeball response in a signal which features ease recording and application in biomedical areas, specialist as Neuro-ophthalmologists, ophthalmologists and optometrist, and even for medical education.

1. Load perturbation responses can violate the law of reciprocal innervation between antagonist muscles under particular conditions. Thus flexor and extensor muscles of wrist and elbow joints are reflexly coactivated by the impact of a ball on the hand during a catching task. The aim of this study was to determine whether reflex coactivation can be preset within the central nervous system (CNS) or whether it is entirely due to the peripheral stimulus. To this end, we studied the behavior of stretch reflex responses of arm muscles evoked by torque motor perturbations applied before and during the catching task. 2. Subjects were instructed to catch a ball dropped from 1.6 m. A torque motor delivered perturbations to the elbow joint, resulting in angular motion at both elbow and wrist joints because of their dynamic mechanical coupling. Two series of experiments were performed that differed in the perturbation waveform. In the first series, a single torque pulse could be randomly applied at different times during the task. The corresponding responses were recovered by subtracting the average of the unperturbed trials from the averages of perturbed trials. In the second series of experiments, a train of pseudorandom pulses was applied continuously during each trial. The time-varying impulse responses were computed at 20-ms intervals by cross-correlation methods. 3. The pattern of the short-latency electromyographic responses evoked by either single pulses or pseudorandom perturbations obeyed the law of reciprocal innervation of antagonist muscles under basal conditions. However, the pattern of the responses evoked by the same perturbations around the time of ball impact on the hand consisted of a substantial coactivation of both stretched and shortening muscles. Reflex coactivation resulted from response patterns that differed at different joints. At the elbow, reflex coactivation resulted from a transient reversal of the direction of the short-latency responses of flexor muscles, with little changes of the responses of extensor muscles. At the wrist, instead, reflex coactivation resulted from simultaneous changes in the response waveform of both flexor and extensor muscles. 4. The peripheral conditions associated with the applied perturbations were constant before the time of ball impact. Thus, because the changes of the stretch reflex responses began before that time, they must have been generated within the CNS. It is here hypothesized that the reversal of the reflex responses is centrally gated by switching from the pathways of reciprocal inhibition to those of coactivation of antagonist alpha-motoneurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Background Essential tremor (ET) is the most common movement disorder and its pathophysiology is unknown. We hypothesize that increased membrane excitability in motor circuits has a key role in the pathogenesis of ET. Specifically, we propose that neural circuits controlling ballistic movements are inherently unstable due to their underlying reciprocal innervation. Such instability is enhanced by increased neural membrane excitability and the circuit begins to oscillate. These oscillations manifest as tremor. Methods Postural limb tremor was recorded in 22 ET patients and then the phenotype was simulated with a conductance-based neuromimetic model of ballistic movements. The model neuron was Hodgkin-Huxley type with added hyperpolarization activated cation current (Ih), low threshold calcium current (IT), and GABA and glycine mediated chloride currents. The neurons also featured the neurophysiological property of rebound excitation after release from sustained inhibition (post-inhibitory rebound). The model featured a reciprocally innervated circuit of neurons that project to agonist and antagonist muscle pairs. Results Neural excitability was modulated by changing Ih and/or IT. Increasing Ih and/or IT further depolarized the membrane and thus increased excitability. The characteristics of the tremor from all ET patients were simulated when Ih was increased to ~10× the range of physiological values. In contrast, increasing other membrane conductances, while keeping Ih at a physiological value, did not simulate the tremor. Increases in Ih and IT determined the frequency and amplitude of the simulated oscillations. Conclusion These simulations support the hypothesis that increased membrane excitability in potentially unstable, reciprocally innervated circuits can produce oscillations that resemble ET. Neural excitability could be increased in a number of ways. In this study membrane excitability was increased by up-regulating Ih and IT. This approach suggests new experimental and clinical ways to understand and treat common tremor disorders.

We investigated the immediate and long-term changes in static eye alignment with acute superior oblique palsy (SOP) in the monkey. When the paretic eye was patched immediately after the lesion for 6–9 days, vertical alignment slowly improved. When the patch was removed and binocular viewing was allowed, alignment slowly worsened. In contrast when a monkey was not patched immediately after the lesion vertical alignment did not improve. We also show that a model of the eye plant can reproduce the observed acute deficit induced by SOP, but only by abandoning Robinson's symmetric simplification of the reciprocal innervation relationship within pairs of agonist–antagonist muscles. The model also demonstrated that physiologic variability in orbital geometry can have a large impact on SOP deficits.

In 1932 Sherrington and Adrian were awarded the Nobel Prize in Physiology or Medicine "for their discoveries regarding the functions of neurons" and in 1944 Erlanger and Gasser were awarded the same prize "for their discoveries relating to the highly differentiated functions of single nerve fibres." Sherrington made important discoveries on the reflex functions of the spinal cord, formulated the concept of the "synapse," defined the principle of the "final common path," studied "reciprocal innervation" and showed that central inhibition was an active phenomenon. He distinguished three types of receptors: extero-, intero-, and proprioceptive, studied the proprioceptive reflexes in the decerebrate animal and mapped their pathways in the spinal cord. Adrian made fundamental discoveries on the function of single nerve fibers, developed new techniques for the amplification of the weak signals and discovered that increased stimulation resulted in increased frequency of the impulses, the amplitude being unaffected. Erlanger and Gasser introduced the cathode-ray oscillograph and demonstrated the existence of three main groups of nerve fibers, A, B, and C, the conduction velocities of which were in approximately linear relationship with the fiber diameter, the A-fibers being the fastest and thickest and the C-fibers the slowest and having the finest diameter. Together the contributions by the four Laureates paved the way to modern neurophysiology.

Since muscle coactivation increases the stiffness and stability of a joint, greater coactivation is likely during faster than slower movements. Very few studies, though, have been conducted to verify this hypothesis. Moreover, a large number of studies have examined coactivation of muscles surrounding the knee joint whereas there are few reports on the elbow joint. The aim of this study was therefore to compare the antagonist activation of the elbow flexors and extensors during isokinetic concentric exercises and to investigate the influence of angular velocity on their activation. Twelve men participated in the study. The surface electromyographic signals (sEMG) were recorded from the biceps brachii (BB) and triceps brachii (TB) muscles during three maximal voluntary isometric contractions (MVC) of elbow flexors and extensors and a set of three maximal elbow flexions and extensions each at 15 degrees, 30 degrees , 60 degrees, 120 degrees, 180 degrees, and 240 degrees.s(-1). Normalized root mean square (RMS) of sEMG was calculated during the isokinetic phase of movement as an index of sEMG amplitude. During elbow flexion, the antagonist activation of BB averaged 16.2% lower than TB, and this difference was statistically significant at all angular velocities. The normalized RMS values ranged from 26.0% +/- 19.0 at MVC to 37.8% +/- 13.9 at 240 degrees.s(-1) for antagonist TB activation, and from 5.7% +/- 5.2 at MVC to 18.9% +/- 8.6 at 240 degrees.s(-1) for antagonist BB activation. No influence of angular velocity on agonist and antagonist activity was found. Moreover, flexion and extension torques were both strongly affected by the amount of antagonist activation. The functional specialization of the two muscle groups could be responsible for the different levels of antagonist activation. The frequent use of BB, which is not assisted by gravity during daily activities, could lead to reduced coactivation due to a better functioning of the control system based upon reciprocal innervation. These findings may have significant implications in the design of rehabilitation programs directed to the elbow joint.

We discovered vasodilator innervation first in canine cerebral arteries, in which nitric oxide (NO) acts as a neurotransmitter; thus, the nerve is called nitroxidergic. Then, reciprocal innervation of noradrenergic and nitroxidergic nerves in canine peripheral arteries was determined; adrenergic nerve-mediated vasoconstriction is predominant over vasodilatation mediated by NO derived from the nerve. In anesthetized dogs, hypertension induced by NO synthase inhibitors is suppressed by hexamethonium. It is hypothesized that impairment of nitroxidergic nerve function by NO synthase inhibition is mainly involved in the genesis of hypertension.

1. Simultaneous intracellular recordings were made from longitudinal muscle (LM) and circular muscle (CM) cells of guinea-pig distal colon during the peristaltic reflex. 2. Spontaneous rhythmical depolarizations with superimposed action potentials (mean amplitude: 19 +/- 2 mV) were regularly recorded from the LM (mean interval: 7 +/- 1 s). In contrast, in the CM layer, spontaneous action potentials occurred with an irregular frequency. Although spontaneous action potentials in LM were rarely correlated in time with those in CM, spontaneous inhibitory junction potentials (sIJPs) were found to occur synchronously in both muscles (5 out of 27 animals; 19 %). 3. Graded inflation of an intra-luminal balloon or mucosal stimulation oral to the recording electrodes elicited gradeable compound IJPs synchronously in both LM (mean amplitude: 6 +/- 1 mV) and CM (mean amplitude: 9 +/- 1 mV) (descending inhibitory reflex). Evoked IJPs were often followed by action potentials in both muscle layers. 4. Mucosal stimuli applied anal to the recording electrodes elicited compound excitatory junction potentials (EJPs) synchronously in both muscles layers that were often associated with the generation of action potentials. In the LM, evoked EJP amplitudes ranged from 3 mV (subthreshold) to 31 mV (including the action potential) and in the CM from 4 mV (subthreshold) to 44 mV (including the action potential). 5. Apamin (500 nM) reduced the evoked IJP in the CM by 55 % (from 11 +/- 2 to 5 +/- 1 mV), but caused no significant reduction in the LM layer (from 8 +/- 1 to 6 +/- 1 mV). Apamin-resistant IJPs in both muscle layers were likely to be due to nitric oxide, since they were abolished by L-NA (100 microM). 6. Atropine (1 microM) abolished the ascending excitatory reflex in both muscles. 7. Injection of neurobiotin into the LM and CM confirmed that simultaneous intracellular recordings were made from different muscle layers. 8. In conclusion, during the peristaltic reflex, the LM and CM layers receive synchronous inhibitory neuromuscular inputs during descending inhibition and synchronous excitatory neuromuscular inputs during ascending excitation. No evidence was found to support reciprocal innervation.

Electromyographic (EMG) activity of orbicularis oculi and levator palpebrae muscles was recorded to study the origin of involuntary eyelid closure in 33 patients. The evoked blink reflex in all patients and in 23 controls was also studied. To examine the excitability of facial motoneurons and bulbar interneurons in individual patients and to compare the results with EMG findings, R1 and R2 recovery indices were calculated in all subjects, as the average of recovery values at 0.5, 0.3, and 0.21 second interstimulus intervals. Based on EMG patterns, the patients were divided into three subclasses: EMG subclass 1, 10 patients with involuntary discharges solely in orbicularis oculi muscle; EMG subclass 2, 20 patients with involuntary discharges in orbicularis oculi and either involuntary levator palpebrae inhibition or a disturbed reciprocal innervation between orbicularis oculi and levator palpebrae; EMG subclass 3, three patients who did not have blepharospasm, but had involuntary levator palpebrae inhibition in association with a basal ganglia disease. The total patient group showed an enhanced recovery of both R1 and R2 components compared with controls. Although 30 out of 33 patients had blepharospasm (EMG subclasses 1 and 2), R1 recovery index was normal in 64% and R2 recovery index was normal in 54%. Patients with an abnormal R2 recovery index had an abnormal R1 recovery index significantly more often. All patients from EMG subclass 1 had an abnormal R2 recovery index, whereas all patients from EMG subclass 3 had normal recovery indices for both R1 and R2 responses. Seventy five per cent of the patients from EMG subclass 2 had normal recovery indices. The results provide further evidence that physiologically blepharospasm is not a homogeneous disease entity, and indicate that different pathophysiological mechanisms at the suprasegmental, or segmental level, or both are involved.

EMG of involuntary muscle contractions and their correlation with clinical pictures in Huntington's disease disclosed a series of motor disorder from chorea to parkinsonism. Irregular brief contractions appearing reciprocally in flexor or extensor muscles were observed in typical chorea with hypotonia. Tonic nonreciprocal contractions appeared in the rigid form. In athetoid movement or dystonic postures, more slowly nonreciprocal fluctuating contractions appeared. In some cases phasic contractions changed from a reciprocal to nonreciprocal pattern by psychic stress. In contrast to the activation of motoneurons in choreatic movements, involuntary brief suppression of voluntary contraction appears in typical chorea. Difference in involuntary movements and muscle tone may result from quantitative differences in involvement of striatal neurons which are the origin of parallel pathways proposed by DeLong and colleagues.

The clinical findings are described in four patients with Synergistic divergence (SD), an ocular motility disorder which is considered to be a variant of Duane retraction syndrome (DRS). Saccadic velocity studies in three patients demonstrated preserved abducting saccades in the affected eye with equally reduced amplitudes on both attempted abduction and adduction. The preserved saccades on attempted abduction of the affected eye, coupled with electromyographic evidence that shows maintenance of normal reciprocal innervation with respect to gaze on attempted abduction as dictated by Sherrington's law, strongly suggest that the abducens nerve is not necessarily absent or severely hypoplastic in this condition. One patient showed typical DRS in the contralateral eye and had a son with bilateral DRS, attesting to a possible genetic and etiologic relationship between SD and DRS. Three patients underwent strabismus surgery. Review of our surgical results and an analysis of the literature indicate that a crippling procedure to the ipsi lateral lateral rectus muscle, such as extirpation, may be necessary to eliminate simultaneous abduction. Over-correction did not occur following lateral rectus extirpation.

Differences in electromyographic (EMG) activity between brief isometric maximum voluntary contractions under conditions of (1) agonist contraction and (2) agonist-antagonist co-contractions were assessed for elbow flexors (biceps brachii) and elbow extensors (triceps, long head). Expressing maximum EMG co-contraction activity as a ratio of agonist maximum EMG activity of the same muscle yielded EMG ratios consistently below 1.0 ( mean= 0.48for flexion and0.76for extension ). Flexor EMG ratios did not co-vary with elbow position but extensor EMG ratios approached 1.0 or sometimes greater at shorter muscle lengths (elbow extension). Findings were in general accord with Sherrington's original proposal of ‘double reciprocal innervation’. Neural circuitry designed to limit full muscle activation during co-contractions may serve to protect the joint against excessive tangential or compressive forces.

Since Sherrington's convincing demonstration of the reciprocal innervation of opposing muscles, it has generally been thought that antagonist muscles are inactive during most voluntary movements. However, more recent evidence suggests that excitation of Renshaw cells may facilitate antagonist coactivation whereas excitation of Ia inhibitory neurons can induce reciprocal inhibition. A body of evidence has accumulated to indicate some of the circumstances which particularly favour the co-contraction of antagonist muscles. Isometric prehension, either in the precision grip or the power grip, can be shown to be one of the most important examples of antagonist coactivation. Studies of the discharge of single Purkinje cells of the intermediate cerebellar cortex in awake monkeys during performance of a maintained grip revealed that the majority of these neurons are deactivated during antagonist co-contraction. In contrast, other, unidentified neurons of the cerebellar cortex were as a group activated during grasping. It is suggested that the Purkinje cells act to inhibit antagonist muscles during reciprocal inhibition but are themselves inhibited during antagonist coactivation. These results support a suggestion made by Tilney and Pike in 1925 that the cerebellum plays an important role in switching between the coactivation and reciprocal inhibition of antagonist muscles.

A clear pattern of reciprocal innervation was found among the orbicularis oculi and the frontalis muscles in man during voluntary contractions. In contrast, facial afferent input was shown to be devoid of reciprocal action on these muscles. The results indicate a lack of γ control in facial muscles.

A case of unilateral retraction of the eyeball in downward gaze as well as downshoot with the retraction when an outward horizontal movement of the contralateral eye was attempted has been introduced. The case has an exotropia with inability to adduct involved eye. The face turned to the left to minimize diplopia in the primary position. During the retraction, the lid widened slightly. An analyses by electrooculography and electromyography suggested that there was an abnormal neural connection between the vertical recti of the involved eye and the contralateral lateral rectus muscle. Co-contraction of vertical recti and loss of the reciprocal innervation were seen at the involved eye. Surgical treatment for exotropia, and total transplantation of vertical recti to the insertion of the involved medial rectus resulted in a slight reduction of the exotropia with the face straight, but not in the retraction as well as adduction and elevation of the involved eye. Based on the results, a central mechanism to produce above abnormality was described.

In cats anesthetized with alpha-chloralose and urethane, the medulla oblongata was explored with electrical and/or chemical stimulation for vasopressor actions. Chemical stimulation included semimicroinjection of sodium glutamate or microinjection of dl-homocysteic acid (DLH). The dorsal (DM), particularly its dorsomedial (DMM) portion, and the ventrolateral (VLM) regions were found to be most sensitive to both electrical and chemical stimulation. In between these two regions there was an area in the ventral portion of the gigantocellular and the parvocellular reticular nuclei that was sensitive to electrical and somewhat sensitive also to chemical stimulation. The responses to chemical stimulation indicate the existence of perikarya in these three areas for vasopressor actions. The most active response of VLM followed microinjection of DLH into the region of nu. paragigantocellularis lateralis (PGL) and subretrofacial nu. These responses were about 30% greater than those from DM where the most active area was found in the DMM region including the nu. and tractus solitarius. When an extensive area of VLM was lesioned bilaterally with kainic acid (KA, 1 μg/100 nl), the resting systemic arterial blood pressure (SAP) fell 42% and the pressor response on DM stimulation fell by more than 80%. In contrast, after similar KA bilateral destruction of DM the resting SAP fell 38% and the pressor responses from VLM decreased 67%. When only a limited area in the PGL/subretrofacial nu. of the rostral VLM (3–4 pressor sites, 1 mm apart) on one side was lesioned, the resting SAP remained unaltered while the pressor response on the ipsilateral DMM decreased 76%. On the other hand, when a similar smaller KA lesion (3–4 sites) was made in the DMM, although the resting SAP did not change, the pressor response on stimulation of the ipsilateral rostral VLM decreased 28%. Further lesioning of the contralateral DMM then decreased the rostral VLM pressor response 62% without much alternation in the resting SAP. Results of the present experiments are in accordance with our previous results that neuronal perikarya for vasopressor action exist not only in VLM but also in DM (18,34) with the function of VLM slightly predominant over DM. It seems highly possible that reciprocal innervation exists between DM and VLM, at least between DMM and the PGL/subretrofacial nu. region.

Optimal control theory takes into account constraints such as energy and time economies which are relevant to the understanding of biological design. The versional eye tracking system responsible for the extremely rapid and precise movements called saccades, which occur, for example, during reading, seemed a likely biological system in which to test for time optimality. A homeomorphic detailed physiological model was constructed based on quantitative muscle, neuronal and oculomotor characteristcs. It is a sixth-order nonlinear representation which considers reciprocal innervation and the asymmetrical force-velocity relationship of the agonist-antagonist muscle pair that moves the eye. Simulations were done by digital computer, and responses of the model to first-, second-, and third-order time optimal control signals were observed; the major portions of the response trajectories were essentially the same. The model response was then compared with measured human saccadic eye movements, and it was found that this experimental data agreed most completely with the model driven by first-order time optimal control signals. Additionally, electromyographic studies in man and neurophysiological experiments in animals agree in showing that the nervous controller signals during saccades are also of the first-order type. Thus, we can conclude that the saccadic eye movements studied are accurately depicted by a model that yields time optimal responses.

A young female outpatient experienced painful tonic contractions in the right triceps surae muscles as a result of a partial damage of the right peroneal nerve. Electrophysiological recordings of the soleus muscle showed a tonic EMG activity and an hyperexcitability of the monosynaptic H reflex (Hmax/Mmax ratio: 90%). Application of transcutaneous electrical nerve stimulation (TENS, 1–2 min) on the peroneal nerve trunk at the head of the fibula resulted both in a pain relief and in the disappearance of the tonic activity in the muscles supplied by the antagonist nerve. Simultaneously, the Hmax/Mmax ratio decreased to normal values (49%). This was followed by an after-effect lasting more than 30 min. The potential role of an impairment of reciprocal inhibition in the originating mechanism of these troubles is discussed.

This research represents part of a series of investigations into the function of mechanoreceptor feedback in lip motor control for speech. In the present study, precise mechanical stretches were applied to subjects' lips while they held the firing frequency of a given single motor unit relatively constant using audio and visual feedback. Preliminary data indicate that mechanical stimulation produces a range of short and long latency excitatory and inhibitory effects in perioral motor units. Of particular interest are short latency inhibitory effects in the depressor labii inferior and platysma muscles. These short latency inhibitory effects suggest that the central organization of the perioral sensorimotor system may possess a form of reciprocal innervation. The operation of a circuit is described which permits improved experimental control over the timing of stretch application relative to moter unit discharge. Initial data collected with this circuit suggest that it may be effectively used to assess the time course of subthreshold excitability changes associated with individual motor units during their repeated discharge.

The flexors and extensors of the hind limb of the cat were simultaneously activated by stretch of a homolateral flexor muscle or by a nocuous stimulus to the homolateral paw under the conditions of the present experiments, in which the muscles under investigation were maximally retracted after detachment of the tendons from their insertions. The simultaneous activation of flexors and extensors was observed in acute and chronic spinal preparations, and sometimes in decerebrate animals. However, when in such preparations the extensor muscle was made to contract by loading its tendon, stretch of the antagonistic flexor muscles and pinching of the toes of the homolateral leg usually resulted in extensor inhibition and flexor excitation, in agreement with the classical tenet of reciprocal innervation. The reflex figure seems to be to an important extent the result of the inflow of afferent impulses.

Two tracking experiments were carried out to investigate the motor control system in adults with cerebral palsy. The first experiment analysed the frequency response characteristics and the surface electromyogram from biceps brachii and triceps brachii, when the cerebral palsy subjects made isometric contractions during the pursuit tracking task with sine wave targets. Patterns of reciprocal innervation of the antagonists explained the frequency response characteristics of tracking behavior of the cerebral palsy subjects. The second experiment analysed perceived response velocity during the compensatory tracking task by means of magnitude estimation method. Fitting power function to the relation between the input frequency and the perceived response velocity, coefficients of determination for the cerebral palsy subjects were found to be lower than those for the normal subjects. It suggests that the cerebral palsy subjects can discriminate their response velocity less exactly than the normal subjects in manual tracking system.