motoneuron

From fly to man, the Wingless (Wg)/Wnt signaling molecule is essential for both the stability and plasticity of the nervous system. The Drosophila neuromuscular junction (NMJ) has proven to be a useful system for deciphering the role of Wg in directing activity-dependent synaptic plasticity (ADSP), which, in the motoneuron, has been shown to be dependent on both the canonical and the noncanonical calcium Wg pathways. Here we show that the noncanonical planar cell polarity (PCP) pathway is an essential component of the Wg signaling system controlling plasticity at the motoneuron synapse...

Roxithromycin (ROX), a commonly used macrolide antibiotic, is extensively employed in human medicine and livestock industries. Due to its structural stability and resistance to biological degradation, ROX persists as a resilient environmental contaminant, detectable in aquatic ecosystems and food products. However, our understanding of the potential health risks to humans from continuous ROX exposure remains limited. In this study, we used the zebrafish as a vertebrate model to explore the potential developmental toxicity of early ROX exposure, particularly focusing on its effects on locomotor functionality and CaP motoneuron development...

INTRODUCTION: Central nervous system excitability depends on the task performed, muscle group solicited, and contraction type. However, little is known on corticospinal and motoneuronal excitability measured during locomotor exercise. This study aimed at determining the reliability of motor-evoked potentials (MEP) and thoracic motor-evoked potentials (TMEP) in dynamic mode during unfatiguing and fatiguing cycling exercise. METHODS: Twenty-two participants completed four visits...

The physiological mechanisms determining the progressive decline in the maximal muscle torque production capacity during isometric contractions to task failure are known to depend on task demands. Task-specificity of the associated adjustments in motor unit discharge rate (MUDR), however, remains unclear. This study examined MUDR adjustments during different submaximal isometric knee extension tasks to failure. Participants performed a sustained and an intermittent task at 20% and 50% of maximal voluntary torque (MVT), respectively (Experiment 1)...

Spinal cord injury (SCI) presents a complex challenge in neurorehabilitation, demanding innovative therapeutic strategies to facilitate functional recovery. This study investigates the effects of treadmill training on SCI recovery, emphasizing motor function enhancement, neural tissue preservation, and axonal growth. Our research, conducted on a rat model, demonstrates that controlled treadmill exercises significantly improve motor functions post-SCI, as evidenced by improved scores on the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and enhanced electromyography readings...

INTRODUCTION: When an isometric contraction is sustained at a submaximal torque, activation of the motoneuron pool increases, making it difficult to measure neural excitability alterations. Thus, more recently, isometric contractions with maintained electromyographic activity (matched-EMG) are being used to induce fatigue; however, little is known about the neurophysiological adjustments that occur to satisfy the requirements of the task. METHODS: For our study, 16 participants performed a 10-min sustained isometric elbow flexion contraction at 20% maximal voluntary contraction (MVC) torque or the level of integrated biceps brachii EMG recorded at 20% MVC torque...

Altered neuronal excitability and synaptic inputs to motoneurons are part of the pathophysiology of Amyotrophic Lateral Sclerosis. The cAMP/PKA pathway regulates both of them but therapeutic interventions at this level are limited by the lack of knowledge about suitable pharmacological entry points. Here we used transcriptomics on microdissected and in situ motoneurons to reveal the modulation of PKA-coupled receptorome in SOD1(G93A) ALS mice, vs WT, demonstrating the dysregulation of multiple PKA-coupled GPCRs, in particular on vulnerable MNs, and the relative sparing of β-adrenergic receptors...

Introduction Cerebral palsy (CP) is a neurodevelopmental condition that results from an injury to a developing brain. Children with CP fail to execute precise, well-coordinated movements, and excessive muscular co-contraction or co-activation is a prominent attribute of CP. The normal reciprocal relationship between agonists and antagonists during voluntary movements is altered in patients with CP. H-reflex, which is often regarded as the electrical equivalent of the spinal stretch reflex, can be used to examine the overall reflex arc, including the Ia sensory afferent strength and the spinal motoneuron excitability state...

We are studying the mechanisms of H-reflex operant conditioning, a simple form of learning. Modelling studies in the literature and our previous data suggested that changes in the axon initial segment (AIS) might contribute. To explore this, we used blinded quantitative histological and immunohistochemical methods to study in adult rats the impact of H-reflex conditioning on the AIS of the spinal motoneuron that produces the reflex. Successful, but not unsuccessful, H-reflex up-conditioning was associated with greater AIS length and distance from soma; greater length correlated with greater H-reflex increase...

While considerable progress has been made in understanding the neuronal circuits that underlie the patterning of locomotor behaviours such as walking, less is known about the circuits that amplify motoneuron output to enable adaptable increases in muscle force across different locomotor intensities. Here, we demonstrate that an excitatory propriospinal neuron population (V3 neurons, Sim1 + ) forms a large part of the total excitatory interneuron input to motoneurons (∼20%) across all hindlimb muscles...

Reliable prediction of multi-finger forces is crucial for neural-machine interfaces. Various neural decoding methods have progressed substantially for accurate motor output predictions. However, most neural decoding methods are performed in a supervised manner, i.e., the finger forces are needed for model training, which may not be suitable in certain contexts, especially in scenarios involving individuals with an arm amputation. To address this issue, we developed an unsupervised neural decoding approach to predict multi-finger forces using spinal motoneuron firing information...

Motoneuron properties and their firing patterns undergo significant changes throughout development and in response to neuromodulators such as serotonin. Here, we examined the age-related development of self-sustained firing and general excitability of tibialis anterior motoneurons in a young development (7-17 years), young adult (18-28 years) and adult (32-53 years) group, as well as in a separate group of participants taking selective serotonin reuptake inhibitors (SSRIs, aged 11-28 years)...

Amyotrophic lateral sclerosis (ALS) diagnosis relies on signs of progressive damage to both lower motoneuron (LMN), given by clinical examination and electromyography (EMG), and upper motoneuron (UMN), given by clinical examination only. Recognition of UMN involvement, however, is still difficult, so that diagnostic delay often remains too long. Shortening the time to clinical and genetic diagnosis is essential in order to provide accurate information to patients and families, avoid time-consuming investigations and for appropriate care management...

Corticospinal neurons (CSNs) synapse directly on spinal neurons, a diverse assortment of cells with unique structural and functional properties necessary for body movements. CSNs modulating forelimb behavior fractionate into caudal forelimb area (CFA) and rostral forelimb area (RFA) motor cortical populations. Despite their prominence, the full diversity of spinal neurons targeted by CFA and RFA CSNs is uncharted. Here, we use anatomical and RNA sequencing methods to show that CSNs synapse onto a remarkably selective group of spinal cell types, favoring inhibitory populations that regulate motoneuron activity and gate sensory feedback...

Cell signaling based on homeoprotein transfer is a pathway with developmental and physiological functions. For a few transcription factors of this family, primarily ENGRAILED1, ENGRAILED2 and OTX2, their physiological functions have led to therapeutic strategies in animal models of human diseases, including Parkinson's disease, amyotrophic lateral sclerosis, amblyopia and anxiety-related disorders. In mesencephalic dopaminergic neurons which degenerate in Parkinson's disease, ENGRAILED1/2 have cell autonomous activities, but their transducing properties enables their use as therapeutic proteins...

Head grooming in Drosophila consists of repeated sweeps of the legs across the head, comprising regular cycles. We used the GAL4-UAS system to study the effects of overexpressing shibirets1 and of Adar knockdown via RNA interference, on the period of head-grooming cycles in Drosophila. Overexpressing shibirets1 interferes with synaptic vesicle recycling and thus with cell communication, while Adar knockdown reduces RNA editing of neuronal transcripts for a large number of genes. All transgenic flies and their controls were tested at 22° to avoid temperature effects; in wild type, cycle frequency varied with temperature with a Q10 of 1...

"Calling behaviour" is a stereotyped rhythmic motor pattern displayed by female moths, by which they emit the sex pheromone to attract of conspecific males. Calling occurs through a squeezing mechanism based on the turtleneck-like folding and unfolding of the ovipositor cuticle during its telescopic extensions and retractions. This mechanism is under the control of the terminal abdominal ganglion (TAG). By combining anatomical and electrophysiological approaches, here we studied the morpho-functional organisation of the abdominal muscles and the activity of motoneurons from TAG nerve N4-N6 as correlated to the ovipositor movements during calling in the female spongy moth Lymantria dispar ...

Amyotrophic lateral sclerosis (ALS) is a mysterious lethal multisystem neurodegenerative disease that gradually leads to the progressive loss of motor neurons. A recent non-contact dying-back injury mechanism theory for ALS proposed that the primary damage is an acquired irreversible intrafusal proprioceptive terminal Piezo2 channelopathy with underlying genetic and environmental risk factors. Underpinning this is the theory that excessively prolonged proprioceptive mechanotransduction under allostasis may induce dysfunctionality in mitochondria, leading to Piezo2 channelopathy...

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes motoneuron death. Motoneuron excitability dysfunction in ALS is suspected to contribute to motoneuron degeneration. Therefore, mechanisms underlying excitability dysfunction are being thoroughly investigated. A recent publication from Trajano et al. (Trajano, G. S., Orssatto, L. B. R., McCombe, P. A., Rivlin, W., Tang, L., & Henderson, R. D. The Journal of Physiology , 2023) examined temporal changes to persistent inward currents (PICs) in ALS patients...

Key developmental pathways and gene networks underlie the formation of sensory cell types and structures involved in chemosensation, vision and mechanosensation, and of the efferents these sensory inputs can activate. We describe similarities and differences in these pathways and gene networks in selected species of the three main chordate groups, lancelets, tunicates, and vertebrates, leading to divergent development of olfactory receptors, eyes, hair cells and motoneurons. The lack of appropriately posited expression of certain transcription factors in lancelets and tunicates prevents them from developing vertebrate-like olfactory receptors and eyes, although they generate alternative structures for chemosensation and vision...