Stoichiometry of the Heteromeric Nicotinic Receptors of the Renshaw Cell.

Neuronal nicotinic acetylcholine receptors (nAChRs) are pentamers built from a variety of subunits. Some are homomeric assemblies of α subunits, others heteromeric assemblies of α and ß subunits which can adopt two stoichiometries (2α:3ß or 3α:2ß). There is evidence for the presence of heteromeric nAChRs with the two stoichiometries in the CNS, but it has not yet been possible to identify them at a given synapse. The 2α:3ß receptors are highly sensitive to agonists, whereas the 3α:2ß stoichiometric variants, initially described as low sensitivity receptors, are indeed activated by low and high concentrations of ACh. We have taken advantage of the discovery that two compounds (NS9283 and Zn) potentiate selectively the 3α:2ß nAChRs to establish (in mice of either sex) the presence of these variants at the motoneuron-Renshaw cell (MN-RC) synapse. NS9283 prolonged the decay of the two-component EPSC mediated by heteromeric nAChRs. NS9283 and Zn also prolonged spontaneous EPSCs involving heteromeric nAChRs, and one could rule out prolongations resulting from AChE inhibition by NS9283. These results establish the presence of 3α:2ß nAChRs at the MN-RC synapse. At the functional level, we had previously explained the duality of the EPSC by assuming that high ACh concentrations in the synaptic cleft account for the fast component and that spillover of ACh accounts for the slow component. The dual ACh sensitivity of 3α:2ß nAChRs now allows to attribute to these receptors both components of the EPSC.SIGNIFICANCE STATEMENT Heteromeric nicotinic receptors assemble α and ß subunits in pentameric structures, which can adopt two stoichiometries: 3α:2ß or 2α:3ß. Both stoichiometric variants are present in the CNS, but they have never been located and characterized functionally at the level of an identified synapse. Our data indicate that 3α:2ß receptors are present at the spinal cord synapses between motoneurons and Renshaw cells, where their dual mode of activation (by high concentrations of ACh for synaptic receptors, by low concentrations of ACh for extrasynaptic receptors) likely accounts for the biphasic character of the synaptic current. More generally, 3α:2ß nicotinic receptors appear unique by their capacity to operate both in the cleft of classical synapses and at extrasynaptic locations.

Force encoding in muscle spindles during stretch of passive muscle.

Muscle spindle proprioceptive receptors play a primary role in encoding the effects of external mechanical perturbations to the body. During externally-imposed stretches of passive, i.e. electrically-quiescent, muscles, the instantaneous firing rates (IFRs) of muscle spindles are associated with characteristics of stretch such as length and velocity. However, even in passive muscle, there are history-dependent transients of muscle spindle firing that are not uniquely related to muscle length and velocity, nor reproduced by current muscle spindle models. These include acceleration-dependent initial bursts, increased dynamic response to stretch velocity if a muscle has been isometric, and rate relaxation, i.e., a decrease in tonic IFR when a muscle is held at a constant length after being stretched. We collected muscle spindle spike trains across a variety of muscle stretch kinematic conditions, including systematic changes in peak length, velocity, and acceleration. We demonstrate that muscle spindle primary afferents in passive muscle fire in direct relationship to muscle force-related variables, rather than length-related variables. Linear combinations of whole muscle-tendon force and the first time derivative of force (dF/dt) predict the entire time course of transient IFRs in muscle spindle Ia afferents during stretch (i.e., lengthening) of passive muscle, including the initial burst, the dynamic response to lengthening, and rate relaxation following lengthening. Similar to acceleration scaling found previously in postural responses to perturbations, initial burst amplitude scaled equally well to initial stretch acceleration or dF/dt, though later transients were only described by dF/dt. The transient increase in dF/dt at the onset of lengthening reflects muscle short-range stiffness due to cross-bridge dynamics. Our work demonstrates a critical role of muscle cross-bridge dynamics in history-dependent muscle spindle IFRs in passive muscle lengthening conditions relevant to the detection and sensorimotor response to mechanical perturbations to the body, and to previously-described history-dependence in perception of limb position.

Segregation of glutamatergic and cholinergic transmission at the mixed motoneuron Renshaw cell synapse.

In neonatal mice motoneurons excite Renshaw cells by releasing both acetylcholine (ACh) and glutamate. These two neurotransmitters activate two types of nicotinic receptors (nAChRs) (the homomeric α7 receptors and the heteromeric α*ß* receptors) as well as the two types of glutamate receptors (GluRs) (AMPARs and NMDARs). Using paired recordings, we confirm that a single motoneuron can release both transmitters on a single post-synaptic Renshaw cell. We then show that co-transmission is preserved in adult animals. Kinetic analysis of miniature EPSCs revealed quantal release of mixed events associating AMPARs and NMDARs, as well as α7 and α*ß* nAChRs, but no evidence was found for mEPSCs associating nAChRs with GluRs. Bayesian Quantal Analysis (BQA) of evoked EPSCs showed that the number of functional contacts on a single Renshaw cell is more than halved when the nicotinic receptors are blocked, confirming that the two neurotransmitters systems are segregated. Our observations can be explained if ACh and glutamate are released from common vesicles onto spatially segregated post-synaptic receptors clusters, but a pre-synaptic segregation of cholinergic and glutamatergic release sites is also possible.

The Preparation of Oblique Spinal Cord Slices for Ventral Root Stimulation.

Electrophysiological recordings from spinal cord slices have proven to be a valuable technique to investigate a wide range of questions, from cellular to network properties. We show how to prepare viable oblique slices of the spinal cord of young mice (P2 - P11). In this preparation, the motoneurons retain their axons coming out from the ventral roots of the spinal cord. Stimulation of these axons elicits back-propagating action potentials invading the motoneuron somas and exciting the motoneuron collaterals within the spinal cord. Recording of antidromic action potentials is an immediate, definitive and elegant way to characterize motoneuron identity, which surpasses other identification methods. Furthermore, stimulating the motoneuron collaterals is a simple and reliable way to excite the collateral targets of the motoneurons within the spinal cord, such as other motoneurons or Renshaw cells. In this protocol, we present antidromic recordings from the motoneuron somas as well as Renshaw cell excitation, resulting from ventral root stimulation.

Potassium currents dynamically set the recruitment and firing properties of F-type motoneurons in neonatal mice.

In neonatal mice, fast- and slow-type motoneurons display different patterns of discharge. In response to a long liminal current pulse, the discharge is delayed up to several seconds in fast-type motoneurons and their firing frequency accelerates. In contrast, slow-type motoneurons discharge immediately, and their firing frequency decreases at the beginning of the pulse. Here, we identify the ionic currents that underlie the delayed firing of fast-type motoneurons. We find that the firing delay is caused by a combination of an A-like potassium current that transiently suppresses firing on a short time scale and a slowly-inactivating potassium current that inhibits the discharge over a much longer time scale. We then show how these intrinsic currents dynamically shape the discharge threshold and the frequency-input function of fast-type motoneurons. These currents contribute to the orderly recruitment of motoneurons in neonates and might play a role in the postnatal maturation of motor units.

Modeling amyotrophic lateral sclerosis in pure human iPSc-derived motor neurons isolated by a novel FACS double selection technique.

Amyotrophic lateral sclerosis (ALS) is a severe and incurable neurodegenerative disease. Human motor neurons generated from induced pluripotent stem cells (iPSc) offer new perspectives for disease modeling and drug testing in ALS. In standard iPSc-derived cultures, however, the two major phenotypic alterations of ALS--degeneration of motor neuron cell bodies and axons--are often obscured by cell body clustering, extensive axon criss-crossing and presence of unwanted cell types. Here, we succeeded in isolating 100% pure and standardized human motor neurons by a novel FACS double selection based on a p75(NTR) surface epitope and an HB9::RFP lentivirus reporter. The p75(NTR)/HB9::RFP motor neurons survive and grow well without forming clusters or entangled axons, are electrically excitable, contain ALS-relevant motor neuron subtypes and form functional connections with co-cultured myotubes. Importantly, they undergo rapid and massive cell death and axon degeneration in response to mutant SOD1 astrocytes. These data demonstrate the potential of FACS-isolated human iPSc-derived motor neurons for improved disease modeling and drug testing in ALS and related motor neuron diseases.

Firing properties of Renshaw cells defined by Chrna2 are modulated by hyperpolarizing and small conductance ion currents Ih and ISK.

Renshaw cells in the spinal cord ventral horn regulate motoneuron output through recurrent inhibition. Renshaw cells can be identified in vitro using anatomical and cellular criteria; however, their functional role in locomotion remains poorly defined because of the difficulty of functionally isolating Renshaw cells from surrounding motor circuits. Here we aimed to investigate whether the cholinergic nicotinic receptor alpha2 (Chrna2) can be used to identify Renshaw cells (RCs(α2)) in the mouse spinal cord. Immunohistochemistry and electrophysiological characterization of passive and active RCs(α2) properties confirmed that neurons genetically marked by the Chrna2-Cre mouse line together with a fluorescent reporter mouse line are Renshaw cells. Whole-cell patch-clamp recordings revealed that RCs(α2) constitute an electrophysiologically stereotyped population with a resting membrane potential of -50.5 ± 0.4 mV and an input resistance of 233.1 ± 11 MΩ. We identified a ZD7288-sensitive hyperpolarization-activated cation current (Ih) in all RCs(α2), contributing to membrane repolarization but not to the resting membrane potential in neonatal mice. Additionally, we found RCs(α2) to express small calcium-activated potassium currents (I(SK)) that, when blocked by apamin, resulted in a complete attenuation of the afterhyperpolarisation potential, increasing cellular firing frequency. We conclude that RCs(α2) can be genetically targeted through their selective Chrna2 expression and that they display currents known to modulate rebound excitation and firing frequency. The genetic identification of Renshaw cells and their electrophysiological profile is required for genetic and pharmacological manipulation as well as computational simulations with the aim to understand their functional role.

Early intrinsic hyperexcitability does not contribute to motoneuron degeneration in amyotrophic lateral sclerosis.

In amyotrophic lateral sclerosis (ALS) the large motoneurons that innervate the fast-contracting muscle fibers (F-type motoneurons) are vulnerable and degenerate in adulthood. In contrast, the small motoneurons that innervate the slow-contracting fibers (S-type motoneurons) are resistant and do not degenerate. Intrinsic hyperexcitability of F-type motoneurons during early postnatal development has long been hypothesized to contribute to neural degeneration in the adult. Here, we performed a critical test of this hypothesis by recording from identified F- and S-type motoneurons in the superoxide dismutase-1 mutant G93A (mSOD1), a mouse model of ALS at a neonatal age when early pathophysiological changes are observed. Contrary to the standard hypothesis, excitability of F-type motoneurons was unchanged in the mutant mice. Surprisingly, the S-type motoneurons of mSDO1 mice did display intrinsic hyperexcitability (lower rheobase, hyperpolarized spiking threshold). As S-type motoneurons are resistant in ALS, we conclude that early intrinsic hyperexcitability does not contribute to motoneuron degeneration.

Subunit composition and kinetics of the Renshaw cell heteromeric nicotinic receptors.

In Renshaw cells (RCs) of newborn mice, activation of motoneurons elicits a four-component synaptic current (EPSC) mediated by two glutamate receptors and two nicotinic receptors (nAChRs). We have analyzed the nicotinic component of the EPSC which is blocked by dihydro-beta-erythroidine (DHßE) with the dual objective of identifying the nAChR subunits involved and of understanding the kinetics of the response. The sensitivity to DHßE of the peak of the EPSC was differentially affected by genetic deletion of three specific nAChR subunits: α2, ß2 and ß4. The comparison of these effects with published findings on recombinant receptors suggests that, in WT mice, two heteromeric assemblies, α4ß2 and α2ß4, coexist in variable proportions in a given RC. Some results seem to require, however, the involvement of an additional subunit. The effects of DHßE on the decay of the EPSCs were compared in WT mice and in PRiMA(-/-) mice, in which the decay is prolonged by the absence of central acetylcholinesterase. In PRiMA(-/-) mice DHßE shortened the decay of the EPSC. In WT mice it did not alter the decay but reduced the amplitude of both components of the EPSC. The results can be interpreted by assuming that the nAChRs exist in two stoichiometries, subsynaptic "low sensitivity" nAChRs and extrasynaptic "high sensitivity" nAChRs activated by spillover.

Near-complete adaptation of the PRiMA knockout to the lack of central acetylcholinesterase.

Acetylcholinesterase (AChE) rapidly hydrolyzes acetylcholine. At the neuromuscular junction, AChE is mainly anchored in the extracellular matrix by the collagen Q, whereas in the brain, AChE is tethered by the proline-rich membrane anchor (PRiMA). The AChE-deficient mice, in which AChE has been deleted from all tissues, have severe handicaps. Surprisingly, PRiMA KO mice in which AChE is mostly eliminated from the brain show very few deficits. We now report that most of the changes observed in the brain of AChE-deficient mice, and in particular the high levels of ambient extracellular acetylcholine and the massive decrease of muscarinic receptors, are also observed in the brain of PRiMA KO. However, the two groups of mutants differ in their responses to AChE inhibitors. Since PRiMA-KO mice and AChE-deficient mice have similar low AChE concentrations in the brain but differ in the AChE content of the peripheral nervous system, these results suggest that peripheral nervous system AChE is a major target of AChE inhibitors, and that its absence in AChE- deficient mice is the main cause of the slow development and vulnerability of these mice. At the level of the brain, the adaptation to the absence of AChE is nearly complete.

Mechanisms shaping the slow nicotinic synaptic current at the motoneuron-renshaw cell synapse.

In spinal cord slices from newborn mice we have analyzed the kinetics of the EPSCs mediated by heteromeric nicotinic receptors at the motoneuron-Renshaw cell (MN-RC) synapse. The miniature EPSCs decay with a time constant of 13.0 ± 1.1 ms whereas the decay of the evoked EPSCs (eEPSCs) is biphasic, with time constants of 15.6 ± 0.8 and 124.8 ± 9.0 ms. The slow component becomes prominent during a repetitive stimulation, but its time constant is unchanged. It is selectively reduced by the addition of acetylcholinesterase (AChE), and thus appears to involve ACh spillover. The constancy of the slow time constant during a train is best explained by a local spillover activating high-affinity receptors. In many cells a fraction of the eEPSC originates in neighboring RCs and is transmitted by the low-pass filter of the gap junctions. The component transmitted electrically can be eliminated by meclofenamic acid, a blocker of gap junctions. The local spillover produced by a repetitive stimulation was compared with the long-range spillover produced by inactivation of AChE. The pharmacological inactivation of AChE by neostigmine caused the appearance of an ultra-slow (second range) decay component in eEPSCs and also a continuous inward current interpreted as resulting from a continuous ACh presence. In animals lacking functional AChE in the CNS (PRiMA(-/-) mice) the EPSCs resembled those observed in neostigmine but the steady inward current was much smaller, suggesting an adaptation to the absence of AChE.

Is early weight bearing resumption beneficial after total hip replacement?

OBJECTIVE: Current rehabilitation protocols of patients following total hip replacement recommend weight bearing on the operated extremity as early as possible. This strategy is likely to induce specific consequences on postural balance control; this study seeks to highlight these reactions to early loading. MATERIALS AND METHODS: Eight men and six women, ranging in age from 57 to 85 years, volunteered enrolling this study on their arrival at our rehabilitation center. This study assessed their postural behavior using a system composed of two separate force platforms under two loading situations; in the course of these tests they were required to minimize their body sway as much as possible by keeping their eyes open. In the natural uncontrolled situation, the subjects adopted a comfortable body weight distribution. In the imposed (IMP) situation, they had to load their operated extremity more than in regular natural conditions in order to distribute their body weight more evenly. Three successive 32-s trials (sampled at 64 Hz) with intermediate recovery periods of equivalent duration were performed allowing period of rest between each trial. The balance strategies were evaluated through a frequency analysis of the resultant and plantar centers of pressure (CP(Res)) of each foot and of the estimated trajectories of the vertical projection of the center of gravity (CG), and from the difference CP(Res)-CG. RESULTS: No difference was found for the plantar CP trajectories in the situation where body weight is spontaneously distributed, whereas loading the implanted extremity induced increased CP(Res), CG, and CP(Res)-CG trajectory amplitudes along the mediolateral axis. No effect was observed along the anteroposterior axis. Finally, when comparing the two limbs for each testing condition, the statistical analysis demonstrated greater displacements along the ML axis for the trajectories measured under the healthy leg than under the implanted extremity. DISCUSSION: Loading the operated extremity early in the rehabilitation process leads to less stability (an increase in the CG movements) and to increased energy expenditure (an increase in the CP(Res)-CG movements). These postural behavior alterations can be explained by various factors including a loss of muscle strength, residual apprehension due to the disuse of this limb, and persistent pain, all of which are increased by limb loading. These features should be taken into consideration when elaborating the rehabilitation protocol for these patients.

Four excitatory postsynaptic ionotropic receptors coactivated at the motoneuron-Renshaw cell synapse.

Renshaw cells (RCs) are spinal interneurons excited by collaterals of the axons of motoneurons (MNs). They respond to a single motoneuronal volley by a surprisingly long (tens of milliseconds) train of action potentials. We have analyzed this synaptic response in spinal cord slices of neonatal mice in light of recent observations suggesting that the MN axons release both acetylcholine and glutamate. We found that the RC synaptic current involves four components of similar amplitudes mediated by two nicotinic receptors (nAChRs, tentatively identified as alpha(7) homomers and alpha(4)beta(2) heteromers) and two glutamate receptors (AMPARs and NMDARs). The decay time constants of the four components cover a wide range: from 3.6 +/- 2.2 ms (alpha(7) nAChRs) to 54.6 +/- 19.5 ms (NMDARs, at -45 mV). The RC discharge can be separated into an initial doublet of high-frequency action potentials followed by later spikes with a variable latency and longer interspike intervals. The initial doublet involves the four ionotropic receptors as well as endogenous voltage-dependent conductances. The late discharge depends on NMDARs, but these receptors must be primed by the initial depolarization. The activation of the NMDARs is prolonged by the fact that their slow deactivation is further slowed by depolarization. The formation of the initial doublet is favored by hyperpolarization, whereas the late discharge is favored by depolarization. This suggests that in physiological conditions the pattern of discharge of the RC in response to a MN input may alternate between a phasic and a tonic response.

Extending cable theory to heterogeneous dendrites.

Dendrites may exhibit many types of electrical and morphological heterogeneities at the scale of a few micrometers. Models of neurons, even so-called detailed models, rarely consider such heterogeneities. Small-scale fluctuations in the membrane conductances and the diameter of dendrites are generally disregarded and spines merely incorporated into the dendritic shaft. Using the two-scales method known as homogenization, we establish explicit expressions for the small-scale fluctuations of the membrane voltage, and we derive the cable equation satisfied by the voltage when these fluctuations are averaged out. This allows us to rigorously establish under what conditions a heterogeneous dendrite can be approximated by a homogeneous cable. We consider different distributions of synapses, orderly or random, on a passive dendrite, and we investigate when replacing excitatory and inhibitory synaptic conductances by their local averages leads to a small error in the voltage. This indicates in which regimes the approximations made in compartmental models are justified. We extend these results to active membranes endowed with voltage-dependent conductances or NMDA receptors. Then we examine under which conditions a spiny dendrite behaves as a smooth dendrite. We discover a new regime where this holds true, namely, when the conductance of the spine neck is small compared to the conductance of the synapses impinging on the spine head. Spines can then be taken into account by an effective excitatory current, the capacitance of the dendrite remaining unchanged. In this regime, the synaptic current transmitted from a spine to the dendritic shaft is strongly attenuated by the weak coupling conductance, but the total current they deliver can be quite substantial. These results suggest that pedunculated spines and stubby spines might play complementary roles in synaptic integration. Finally, we analyze how varicosities affect voltage diffusion in dendrites and discuss their impact on the spatiotemporal integration of synaptic input.

Postnatal electrical and morphological abnormalities in lumbar motoneurons from transgenic mouse models of amyotrophic lateral sclerosis.

Antidromically identified lumbar motoneurons intracellularly recorded in the entire brainstem/spinal cord preparation isolated from SOD1(G85R) postnatal mice (P3-P10) were labelled with neurobiotin and fully reconstructed in 3D from serial sections in order to analyse their morphology. This staining procedure revealed differences between WT and SOD1(G85R) dendritic trees for most metric and topologic parameters analyzed. A highly complex morphology of SOD1(G85R) motoneurons dendrites (increased number of branching points and terminations) was found and the dendritic trees were longer compared to the WT motoneurons. These morphological changes observed in P8-P9 motoneurons mice occurred concomitantly with a decrease in the input resistance and gain. During electrophysiological recordings, four patterns of discharge were observed in response to ramp stimulations, that were equally distributed in WT and SOD1(G85R) motoneurons. In slice preparation, whole cell patch-clamp recordings made from developing motoneurons in SOD1(G85R) and double transgenic SOD1(G93A)/Hb9-eGFP mice showed that Riluzole, a blocker of persistent inward sodium conductance, altered the repetitive firing in a similar way for the 2 strains. These results show that the SOD1 mutations linked to familial ALS alter the development of the electrical and morphological properties of lumbar motoneurons.

[What compensatory motor strategies do patients with multiple sclerosis develop for balance control?]. / Quelles stratégies motrices de compensation les patients souffrant d'une sclérose en plaques sont-ils capables de développer pour contrôler leur équilibre?

INTRODUCTION: One of the main features of multiple sclerosis (MS) is the deterioration of motor pathway axons, and in some cases, sensory system axons. Consequently, experimental sensori-motor testing with the undisturbed upright stance paradigm might be useful. It can be hypothesized that the postural strategies could be differently affected depending on the degree of dysfunction of both sensory and motor tracts. METHODS: Twelve and fifteen patients, classified from sensory clinical tests as ataxo-spastic (SEP-AS) or only spastic (SEP-S), respectively were included in this study and compared to 12 healthy adults matched for age. The postural strategies were assessed from the centre of pressure trajectories (CP), measured from the force platform on which the subjects were instructed to stand upright eyes open for a trial lasting 51.2 s. biomechanical modelling was applied to these trajectories to compute the movements of the centre of gravity (CG) and consequently, the vertical difference between the CP and then the CP-CG, two elementary movements known to characterize postural performance movements for CGv and horizontal acceleration communicated to the CG for the CP-CG movements, and consequently overall neuro-muscular activity. To estimate the relative contribution of each of these elementary movements, an analysis based on frequency parameters (RMS and MF) was conducted. RESULTS: Both SEP-AS and SEP-S groups demonstrate larger CG and CP-CG movements than the age paired individuals. However, some statistically significant differences has to be emphasised between the two MS subgroups but only for the CP-CG component: the RMS of these movements are largely increased for the SEP-AS group, as compared to the SEP-S one. Biomechanically, this feature expresses the necessity for these very patients to produce exaggerated horizontal forces, and thus an increased energy expenditure, to handle the CG movements. The lack of effect observed for the CG movements underlines the capacity for the SEP-AS group to set appropriate control mechanisms for counteracting these less favourable initial conditions. CONCLUSION: By demonstrating specific trends in the postural organisation aimed at controlling undisturbed upright stance maintenance, this study can be of interest for the practitioner by legitimating this experimental paradigm as a simple and non invasive way to diagnose appropriately the sensori-motor deficiency.

How proprioceptive impairments affect quiet standing in patients with multiple sclerosis.

To assess if multiple sclerosis patients with proprioceptive impairment are specifically affected during quiet standing with eyes open and how they can develop motor compensatory processes, 56 patients, classified from sensory clinical tests as ataxo-spastic (MS-AS) or only having spasticity (MS-S), were compared to 23 healthy adults matched for age. The postural strategies were assessed from the centre-of-pressure trajectories (CP), measured from a force platform in the eyes open standing condition for a single trial lasting 51.2 s. The vertical projection of the centre of gravity (CGv) and its vertical difference from the CP (CP-CGv) were then estimated through a biomechanical relationship. These two movements permit the characterization of the postural performance and the horizontal acceleration communicated to the CG and from that, the global energy expenditure, respectively. Both MS-AS and MS-S groups demonstrate larger CGv and CP-CGv movements than healthy individuals of the same age. Whilst similar CGv values are noticed in both MS subgroups, suggesting similar postural performances, statistically significant differences are observed for the CP-CGv component. Biomechanically, this feature expresses the necessity for the MS-AS group to develop augmented neuro-muscular means to control their body movements, as compared to the MS-S group. By demonstrating for both groups of patients similar postural performance accompanied by a varying degree of energy expenditure to maintain undisturbed upright stance, this study reveals that MS-AS patients which are affected by proprioceptive loss can compensate for this deficit with more efficient control strategies, when standing still with their eyes open.

[Clinical and posturographic comparison of patients with recent total hip arthroplasty]. / Evolution comparée des tests cliniques et posturographiques lors de la rééducation des arthroplasties totales de hanche.

PURPOSE OF THE STUDY: To highlight the congruence of clinical and posturographic tests in patients undergoing hip arthroplasty. MATERIAL AND METHODS: Ten patients (six males and four females) were included in this study and tested when at admission and discharge from the rehabilitation department (12 and 27 days after surgery respectively). The patients were asked to stand undisturbed in the upright position, eyes closed on a system composed of two force platforms. Five successive 32s trials (sampled at 64 Hz) were conducted with rest intervals of similar duration between trials. The plantar center of pressure (CP), displacements, and resultant CP (CPRes) were then computed and analyzed in various ways. In parallel, various clinical tests, including muscular force, hip range of motion, walking speed, functional independence, pain, sensitivity, lateral reach, and get up and go aimed at evaluating global coordination. Correlations, using the non-parametric Spearman coefficient, were computed from the differences between clinical and posturographic parameters obtained at admission and discharge from the rehabilitation department. RESULTS: Certain statistically significant differences in postural behavior was observed both for clinical and posturographic tests between admission and discharge. Body weigh distribution over the two legs was largely asymmetric at onset and, though it declined, persisted at discharge. There was not difference for the mean positions of both the plantar CP and the resultant of the CP movements. On the contrary, it was noteworthy that the variances of CP displacements (data dispersion) were initially larger on the sound leg along the anteroposterior axis and that this compensatory feature disappeared at the end of the stay. At discharge, the variances computed from the sound and the prosthetic limb became equivalent. All the clinical tests demonstrated statistically significant improvements in results at discharge compared with admission. Several significant correlations involving clinical tests and mean positions along the anteroposterior axis, the degree of body weight asymmetry and variances along both the mediolateral and anteroposterior axes were found. DISCUSSION: These results enable a better understanding of strategies used by hip arthroplasty patients to keep balance. Even though their sensitivity was quite different, both clinical and posturographic measurements demonstrated their ability to assess recovery from surgery. These two evaluation techniques are complementary.

Early electrophysiological abnormalities in lumbar motoneurons in a transgenic mouse model of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis is a lethal, adult-onset disease characterized by progressive degeneration of motoneurons. Recent data have suggested that the disease could be linked to abnormal development of the motor nervous system. Therefore, we investigated the electrical properties of lumbar motoneurons in an in-vitro neonatal spinal cord preparation isolated from SOD1(G85R) mice, which is a transgenic model of amyotrophic lateral sclerosis. The study was performed on young animals at the beginning of their second week, between postnatal days 6 and 10. Measurements of resting membrane potential and action potential characteristics of motoneurons were similar in wild-type and SOD1(G85R) mice. However, the input resistance of motoneurons from transgenic mice was significantly lower than that of wild-type animals, whereas their membrane capacitance was increased, strongly suggesting larger SOD1(G85R) motoneurons. Furthermore, the slope of the frequency-intensity curve was steeper in motoneurons from wild-type pups. Interestingly, the input resistance as well as the slope of the frequency-intensity curves of other spinal neurons did not show such differences. Finally, the amplitude of dorsal root-evoked potentials following high-intensity stimulation was significantly smaller in SOD1(G85R) motoneurons. The superoxide dismutase 1 mutation thus induces specific alterations of the functional properties of motoneurons early in development.

[Efficacy of intrathecal baclofen in the treatment of spasticity in stroke]. / Intérêt de la pompe à baclofène dans le traitement de la spasticité chez l'hémiplégique: à propos d'un cas.

OBJECTIVE: To determine whether intrathecal administration of baclofen reduced spastic hypertonia in a hemiplegic patient after hemorrhagic stroke. METHODS: A trial of intrathecal administration of baclofen was carried out with bolus injections of 50 and 75 microg baclofen and clinical and functional evaluation (Aschworth, articular amplitude) before and after injection in a patient with hemorrhagic stroke. After these trials, the placement of a pump was proposed to the patient. RESULTS: Aschworth score improved from 4 to 3 on triceps, quadriceps and adductus, with functional improvement of gait quality and perimeter and position in the wheelchair. Cephalgia, present before the treatment, increased after the implantation of the pump. The patient had some ejaculation trouble with the treatment, as well as some neurological pains after the pump implantation but experienced no effect on upper limbs. DISCUSSION: The intrathecal administration of baclofen has been used in some studies of hemiplegic patients, with reduced spasticity and improved the kinematic parameters of gait. The intrathecal baclofen administration could complement other treatment to control spasticity after stroke. CONCLUSION: Intrathecal baclofen administration could be an interesting complementary therapeutic among patients with important spasticity not controlled by the usual treatments.