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Primary motor cortex (M1) network stability depends on activity of inhibitory interneurons, for which susceptibility to stress was previously demonstrated in limbic regions. Hyperexcitability in M1 following changes in the excitatory/inhibitory balance is a key pathological hallmark of amyotrophic lateral sclerosis (ALS). Using electrophysiological approaches, we assessed the impact of acute restraint stress on inhibitory interneurons excitability and global synaptic plasticity in M1 of the SOD1G93A ALS mouse model at a late pre‐symptomatic stage (10–12.5 weeks). Based on their firing type (continuous, discontinuous, with accommodation or not) and electrophysiological characteristics (resting potential, rheobase, firing frequency), interneurons from M1 slices were separated into four clusters, labelled from 1 to 4. Among them, only interneurons from the first cluster, presenting continuous firing with few accommodations, tended to show increased excitability in wild‐type (WT) and decreased excitability in SOD1G93A animals following stress. In vivo analyses of evoked field potentials showed that stress suppressed the theta burst‐induced plasticity of an excitatory component (N1) recorded in the superficial layers of M1 in WT, with no impact on an inhibitory complex (N2–P1) from the deeper layers. In SOD1G93A mice, stress did not affect N1 but suppressed the N2–P1 plasticity. These data suggest that stress can alter M1 network functioning in a different manner in WT and SOD1G93A mice, possibly through changes of inhibitory interneurons excitability and synaptic plasticity. This suggests that stress‐induced activity changes in M1 may therefore influence ALS outcomes. Key points: Disruption of the excitatory/inhibitory balance in the primary motor cortex (M1) has been linked to cortical hyperexcitability development, a key pathological hallmark of amyotrophic lateral sclerosis (ALS).Psychological stress was reported to influence excitatory/inhibitory balance in limbic regions, but very little is known about its influence on the M1 functioning under physiological or pathological conditions.Our study revealed that acute stress influences the excitatory/inhibitory balance within the M1, through changes in interneurons excitability along with network plasticity. Such changes were different in pathological (SOD1G93A ALS mouse model) vs. physiological (wild‐type) conditions.The results of our study help us to better understand how stress modulates the M1 and highlight the need to further characterize stress‐induced motor cortex changes because it may be of importance when evaluating ALS outcomes. [ABSTRACT FROM AUTHOR]

Traditional myoelectric controls of trans-humeral prostheses fail to provide intuitive coordination of the necessary degrees of freedom. We previously showed that by using artificial neural network predictions to reconstruct distal joints, based on the shoulder posture and movement goals (i.e., position and orientation of the targeted object), participants were able to position and orient an avatar hand to grasp objects with natural arm performances. However, this control involved rapid and unintended prosthesis movements at each modification of the movement goal, impractical for real-life scenarios. Here, we eliminate this abrupt change using novel methods based on an angular trajectory, determined from the speed of stump movement and the gap between the current and the 'goal' distal configurations. These new controls are tested offline and online (i.e., involving participants-in-the-loop) and compared to performances obtained with a natural control. Despite a slight increase in movement time, the new controls allowed twelve valid participants and six participants with trans-humeral limb loss to reach objects at various positions and orientations without prior training. Furthermore, no usability or workload degradation was perceived by participants with upper limb disabilities. The good performances achieved highlight the potential acceptability and effectiveness of those controls for our target population. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a fatal adult‐onset neurodegenerative disease characterized by progressive motor neuron degeneration and muscle paralysis. Recent evidence suggests the dysfunction of inhibitory signalling in ALS motor neurons. We have shown that embryonic day (E)17.5 spinal motoneurons (MNs) of the SOD1G93A mouse model of ALS exhibit an altered chloride homeostasis. At this prenatal stage, inhibition of spinal motoneurons (MNs) is mediated by depolarizing GABAergic/glycinergic postsynaptic potentials (dGPSPs). Here, using an ex vivo preparation and patch clamp recording from MNs with a chloride equilibrium set below spike threshold, we report that low input resistance (Rin) E17.5 MNs from the SOD1G93A ALS mouse model do not correctly integrate dGPSPs evoked by electrical stimulations of GABA/glycine inputs at different frequencies. Indeed, firing activity of most wild‐type (WT) MNs with low Rin was inhibited by incoming dGPSPs, whereas low Rin SOD1G93A MNs were excited or exhibited a dual response (excited by low frequency dGPSPs and inhibited by high frequency dGPSPs). Simulation highlighted the importance of the GABA/glycine input density and showed that pure excitation could be obtained in SOD‐like MNs by moving GABA/glycine input away from the cell body to dendrites. This was in agreement with confocal imaging showing a lack of peri‐somatic inhibitory terminals in SOD1G93A MNs compared to WT littermates. Putative fast ALS‐vulnerable MNs with low Rin are therefore lacking functional inhibition at the near‐term prenatal stage. Key points: We analysed the integration of GABAergic/glycinergic synaptic events by embryonic spinal motoneurons (MNs) in a mouse model of the amyotrophic lateral sclerosis (ALS) neurodegenerative disease.We found that GABAergic/glycinergic synaptic events do not properly inhibit ALS MNs with low input resistance, most probably corresponding to future vulnerable MNs.We used a neuron model to highlight the importance of the GABA/glycine terminal location and density in the integration of the GABAergic/glycinergic synaptic events.Confocal imaging showed a lack of GABA/glycine terminals on the cell body of ALS MNs.The present study suggests that putative ALS vulnerable MNs with low Rin lack functional inhibition at the near‐term stage. [ABSTRACT FROM AUTHOR]

Hyperexcitability of spinal reflexes and reduced synaptic inhibition are commonly associated with spasticity after spinal cord injury (SCI). In adults, the activation of γ-aminobutyric [acid.sub.A] ([GABA.sub.A]) and glycine receptors inhibits neurons as a result of low intracellular chloride ([Cl.sup.-]) concentration, which is maintained by the potassium-chloride cotransporter KCC2 (encoded by Slc12a5). We show that KCC2 is downregulated after SCI in rats, particularly in motoneuron membranes, thereby depolarizing the [Cl.sup.-] equilibrium potential and reducing the strength of postsynaptic inhibition. Blocking KCC2 in intact rats reduces the rate-dependent depression (RDD) of the Hoffmann reflex, as is observed in spasticity. RDD is also decreased in KCC2-deficient mice and in intact rats after intrathecal brain-derived neurotrophic factor (BDNF) injection, which downregulates KCC2. The early decrease in KCC2 after SCI is prevented by sequestering BDNF at the time of SCI. Conversely, after SCI, BDNF upregulates KCC2 and restores RDD. Our results open new perspectives for the development of therapeutic strategies to alleviate spasticity., Spasticity is a disabling complication affecting individuals with SCI [1]. About 75% of individuals with SCI show spasticity 1 year after injury, and about half of them receive antispasticity medication. [...]

Objective: We investigated how participants controlling a humanoid robotic arm's 3D endpoint position by moving their own hand are influenced by the robot's postures. We hypothesized that control would be facilitated (impeded) by biologically plausible (implausible) postures of the robot. Background: Kinematic redundancy, whereby different arm postures achieve the same goal, is such that a robotic arm or prosthesis could theoretically be controlled with less signals than constitutive joints. However, congruency between a robot's motion and our own is known to interfere with movement production. Hence, we expect the human-likeness of a robotic arm's postures during endpoint teleoperation to influence controllability. Method: Twenty-two able-bodied participants performed a target-reaching task with a robotic arm whose endpoint's 3D position was controlled by moving their own hand. They completed a two-condition experiment corresponding to the robot displaying either biologically plausible or implausible postures. Results: Upon initial practice in the experiment's first part, endpoint trajectories were faster and shorter when the robot displayed human-like postures. However, these effects did not persist in the second part, where performance with implausible postures appeared to have benefited from initial practice with plausible ones. Conclusion: Humanoid robotic arm endpoint control is impaired by biologically implausible joint coordinations during initial familiarization but not afterwards, suggesting that the human-likeness of a robot's postures is more critical for control in this initial period. Application: These findings provide insight for the design of robotic arm teleoperation and prosthesis control schemes, in order to favor better familiarization and control from their users. [ABSTRACT FROM AUTHOR]

Cd2+ affects the gating properties of I(sub AB) channels, the hyperpolarization-activated K+ -mediated currents, by interfering with their opening and not with their closing mechanism. In muscle fibers of the crayfish Procambarus clarkii, I(sub AB) is reduced reversibly by extracellular Cd2+ in a concentration-dependent manner. Thus Cd2+ affects the gating of I(sub AB) channels by binding to a site different to that involved in the K+ permeability pathway.