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A sedentary lifestyle can lead to motor and cognitive deficits, increasing the risk of neurodegenerative diseases in ageing. Emerging hypotheses suggest that these functional alterations may be related to energy metabolism. Indeed, ATP produced by mitochondria is essential for muscle contraction, neurotransmission and brain plasticity processes. Although a sedentary lifestyle has been associated with mitochondrial alterations in skeletal muscle, the potential effects on brain structures have yet to be investigated. The present study aimed to determine whether early sensorimotor restriction (SMR) alters mitochondrial metabolism in rat muscles and brain structures. Enzyme activities of citrate synthase (CS) and respiratory chain complexes I, II and IV were measured using a spectrophotometric technique and mitochondrial respiration was assessed using high-resolution respirometry in two hind limb muscles [soleus and extensor digitorum longus (EDL)] and four brain structures (sensorimotor cortex, striatum, prefrontal cortex and hippocampus) in control rats and rats experiencing early SMR from birth to day 28. Mitochondrial enzyme activities decreased in the soleus (complexes I and II), in the EDL (complex I) and in the hippocampus (complexes I and IV) in an age-dependent manner, whereas no effect was observed in other brain structures. CS activity decreases in the soleus and increases transiently in the striatum and sensorimotor cortex at postnatal day 15. Mitochondrial respiration was reduced in the soleus and in the sensorimotor cortex (CI and CI+CII). Early SMR appears to induce quantitative and qualitative mitochondrial alterations in skeletal muscles and certain brain structures involved in cognitive and motor processes. KEY POINTS: Early sensorimotor restriction (SMR) alters mitochondrial enzyme activities and mitochondrial respiration in skeletal muscles and brain. Mitochondrial alterations induced by early SMR are age-dependent, structure-dependent and complex-dependent. Mitochondrial enzyme activities increase during development and the evolution pattern is specific to the different structures., (© 2025 The Author(s). The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Children with neurodevelopmental disorders, such as developmental coordination disorder (DCD), exhibit gross to fine sensorimotor impairments, reduced physical activity and interactions with the environment and people. This disorder co-exists with cognitive deficits, executive dysfunctions and learning impairments. Previously, we demonstrated in rats that limited amounts and atypical patterns of movements and somatosensory feedback during early movement restriction manifested in adulthood as degraded postural and locomotor abilities, and musculoskeletal histopathology, including muscle atrophy, hyperexcitability within sensorimotor circuitry and maladaptive cortical plasticity, leading to functional disorganization of the primary somatosensory and motor cortices in the absence of cortical histopathology. In this study, we asked how this developmental sensorimotor restriction (SMR) started to impact the integration of multisensory information and the emergence of sensorimotor reflexes in rats. We also questioned the enduring impact of SMR on motor activities, pain and memory. SMR led to deficits in the emergence of swimming and sensorimotor reflexes, the development of pain and altered locomotor patterns and posture with toe-walking, adult motor performance and night spontaneous activity. In addition, SMR induced exploratory hyperactivity, short-term impairments in object-recognition tasks and long-term deficits in object-location tasks. SMR rats displayed minor alterations in histological features of the hippocampus, entorhinal, perirhinal and postrhinal cortices yet no obvious changes in the prefrontal cortex. Taken all together, these results show similarities with the symptoms observed in children with DCD, although further exploration seems required to postulate whether developmental SMR corresponds to a rat model of DCD., (© 2024 The Author(s). European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Motor disorders are considered to originate mainly from brain lesions. Placental dysfunction or maternal exposure to a persistently hypoxic environment is a major cause of further motor disorders such as cerebral palsy. Our main goal was to determine the long-term effects of mild intrauterine acute ischemic stress on rat soleus myofibres and whether erythropoietin treatment could prevent these changes. Rat embryos were subjected to ischemic stress at embryonic day E17. They then received an intraperitoneal erythropoietin injection at postnatal days 1-5. Soleus muscles were collected at postnatal day 28. Prenatal ischemic stress durably affected muscle structure, as indicated by the greater fiber cross-sectional area (+ 18%) and the greater number of mature vessels (i.e. vessels with mature endothelial cells) per myofibres (+ 43%), and muscle biochemistry, as shown by changes in signaling pathways involved in protein synthesis/degradation balance (-81% for 4EBP1; -58% for AKT) and Hif1α expression levels (+ 95%). Erythropoietin injection in ischemic pups had a weak protective effect: it increased muscle mass (+ 25% with respect to ischemic pups) and partially prevented the increase in muscle degradation pathways and mature vascularization, whereas it exacerbated the decrease in synthesis pathways. Hence, erythropoietin treatment after acute ischemic stress contributes to muscle adaptation to ischemic conditions., Competing Interests: Declarations Ethical approval We confirm that all procedures were carried out in accordance with the European Communities Council Directive 2010/63/UE, and were approved by the Regional Committee on the Ethics of Animal Experiments of the Nord Pas-de-Calais region (CEEA 75, reference number: APAFIS#4732-2016031 112395755v7). Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Childhood is a period of construction of the organism, during which interactions with the environment and regular physical activity are necessary for the maturation of the neuronal networks. An atypical sensorimotor activity during childhood (due to bed-rest or neurodevelopmental disorders) impacts the development of the neuromuscular system. A model of sensorimotor restriction (SMR) developed in rats has shown that casting pups' hind limbs from postnatal day 1 (P1) to P28 induced a severe perturbation of motor behavior, due to muscle weakness as well as disturbances within the central nervous system. In the present study, our objective was to determine whether SMR affects the early postnatal ontogenesis. We explored the neuromuscular development through the determination of the age for achievement of the main neurodevelopmental reflexes, which represent reliable indicators of neurological and behavioral development. We also evaluated the maturation of postural control. Our results demonstrate that SMR induces a delay in the motor development, illustrated by a several days delay in the acquisition of a mature posture and in the acquisition reflexes: hind limb grasping, righting, hind limb placing, cliff avoidance, negative geotaxis. In conclusion, impaired physical activity and low interactions with environment during early development result in altered maturation of the nervous system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Interaction with the environment appears necessary for the maturation of sensorimotor and cognitive functions in early life. In rats, a model of sensorimotor restriction (SMR) from postnatal day 1 (P1) to P28 has shown that low and atypical sensorimotor activities induced the perturbation of motor behavior due to muscle weakness and the functional disorganization of the primary somatosensory and motor cortices. In the present study, our objective was to understand how SMR affects the muscle-brain dialogue. We focused on irisin, a myokine secreted by skeletal muscles in response to exercise. FNDC5/irisin expression was determined in hindlimb muscles and brain structures by Western blotting, and irisin expression in blood and cerebrospinal fluid was determined using an ELISA assay at P8, P15, P21 and P28. Since irisin is known to regulate its expression, Brain-Derived Neurotrophic Factor (BDNF) levels were also measured in the same brain structures. We demonstrated that SMR increases FNDC5/irisin levels specifically in the soleus muscle (from P21) and also affects this protein expression in several brain structures (as early as P15). The BDNF level was increased in the hippocampus at P8. To conclude, SMR affects FNDC5/irisin levels in a postural muscle and in several brain regions and has limited effects on BDNF expression in the brain.

Children with low physical activity and interactions with environment experience atypical sensorimotor development and maturation leading to anatomical and functional disorganization of the sensorimotor circuitry and also to enduring altered motor function. Previous data have shown that postnatal movement restriction in rats results in locomotor disturbances, functional disorganization and hyperexcitability of the hind limb representations in the somatosensory and motor cortices, without apparent brain damage. Due to the reciprocal interplay between the nervous system and muscle, it is difficult to determine whether muscle alteration is the cause or the result of the altered sensorimotor behavior (Canu et al., 2019). In the present paper, our objectives were to evaluate the impact of early movement restriction leading to sensorimotor restriction (SMR) during development on the postural soleus muscle and on sensorimotor performance in rats, and to determine whether changes were reversed when typical activity was resumed. Rats were submitted to SMR by hind limb immobilization for 16 h / day from birth to postnatal day 28 (PND28). In situ isometric contractile properties of soleus muscle, fiber cross sectional area (CSA) and myosin heavy chain content (MHC) were studied at PND28 and PND60. In addition, the motor function was evaluated weekly from PND28 to PND60. At PND28, SMR rats presented a severe atrophy of soleus muscle, a decrease in CSA and a force loss. The muscle maturation appeared delayed, with persistence of neonatal forms of MHC. Changes in kinetic properties were moderate or absent. The Hoffmann reflex provided evidence for spinal hyperreflexia and signs of spasticity. Most changes were reversed at PND60, except muscle atrophy. Functional motor tests that require a good limb coordination, i.e. rotarod and locomotion, showed an enduring alteration related to SMR, even after one month of 'typical' activity. On the other hand, paw withdrawal test and grip test were poorly affected by SMR whereas spontaneous locomotor activity increased over time. Our results support the idea that proprioceptive feedback is at least as important as the amount of motor activity to promote a typical development of motor function. A better knowledge of the interplay between hypoactivity, muscle properties and central motor commands may offer therapeutic perspectives for children suffering from neurodevelopmental disorders., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Plasticity of the cerebral cortex following a modification of the sensorimotor experience takes place in several steps that can last from few hours to several months. Among the mechanisms involved in the dynamic modulation of the cerebral cortex in adults, it is commonly proposed that short-term plasticity reflects changes in synaptic connections. Here, we were interested in the time-course of synaptic plasticity taking place in the somatosensory primary cortex all along a 14-day period of sensorimotor perturbation (SMP), as well as during a recovery phase up to 24 h. Activation and expression level of pre- (synapsin 1, synaptophysin, synaptotagmin 1) and postsynaptic (AMPA and NMDA receptors) proteins, postsynaptic density scaffold proteins (PSD-95 and Shank2), and cytoskeletal proteins (neurofilaments-L and M, β3-tubulin, synaptopodin, N-cadherin) were determined in cortical tissue enriched in synaptic proteins. During the SMP period, most changes were observed as soon as D7 in the presynaptic compartment and were followed, at D14, by changes in the postsynaptic compartment. These changes persisted at least until 24 h of recovery. Proteins involved in synapse structure (scaffolding, adhesion, cytoskeletal) were mildly affected and almost exclusively at D14. We concluded that experience-dependent reorganization of somatotopic cortical maps is accompanied by changes in synaptic transmission with a very close time-course., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cerebral palsy (CP) is a complex syndrome of various sensory, motor and cognitive deficits. Its prevalence has recently decreased in some developed countries and its symptoms have also shifted since the 1960s. From the 1990s, CP has been associated with prematurity, but recent epidemiologic studies show reduced or absent brain damage, which recapitulates developmental coordination disorder (DCD). In previous studies, we developed a rat model based on mild intrauterine hypoperfusion (MIUH) that recapitulated the diversity of symptoms observed in preterm survivors. Briefly, MIUH led to early inflammatory processes, diffuse brain damage, minor locomotor deficits, musculoskeletal pathologies, neuroanatomical and functional disorganization of the primary somatosensory (S1) cortex but not in the motor cortex (M1), delayed sensorimotor reflexes, spontaneous hyperactivity, deficits in sensory information processing, and memory and learning impairments in adult rats. Adult MIUH rats also exhibited changes in muscle contractile properties and phenotype, enduring hyperreflexia and spasticity, as well as hyperexcitability in the sensorimotor cortex. We recently developed a rat model of DCD based on postnatal sensorimotor restriction (SMR) without brain damage. Briefly, SMR led to digitigrade locomotion (i.e., "toe walking") related to ankle-knee overextension, degraded musculoskeletal tissues (e.g., gastrocnemius atrophy), and lumbar hyperreflexia. The postnatal SMR then led to secondary degradation of the hind-limb maps in S1 and M1 cortices, altered cortical response properties and cortical hyperexcitability, but no brain damage. Thus, our 2 rat models appear to recapitulate the diversity of symptoms ranging from CP to DCD and contribute to understanding the emergence and mechanisms underlying the corresponding neurodevelopmental disorders. These preclinical models seem promising for testing strategies of rehabilitation based on both physical and cognitive training to promote adaptive brain plasticity and to improve physical body conditions., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: Several studies have shown the importance of phosphorylation, O-GlcNAcylation and their interplay in neuronal processes., New Method: To get understanding about molecular mechanisms of synaptic plasticity, we performed a preparation of synaptic protein-enriched fraction on a small sample of rat sensorimotor cortex. We then optimized a multiplexed proteomic strategy to detect O-GlcNAcylated proteins, phosphoproteins, and the whole proteome within the same bidimensional gel. We compared different protocols (solubilisation buffer, reticulation and composition of the gel, migration buffer) to optimize separating conditions for 2D-gel electrophoresis of synaptic proteins. The O-GlcNAcome was revealed using Click chemistry and the azide-alkyne cycloaddition of a fluorophore on O-GlcNAc moieties. The phosphoproteome was detected by Phospho-Tag staining, while the whole proteome was visualized through SYPRORuby staining., Results: This method permitted, after sequential image acquisition, the direct in-gel detection of O-GlcNAcome, phosphoproteome, and whole proteome of synapse-associated proteins., Conclusion: This original method of differential proteomic analysis will permit to identify key markers of synaptic plasticity that are O-GlcNAcylated and/or phosphorylated, and their molecular regulations in neuronal processes., Competing Interests: Declaration of Competing Interest The authors have declared no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Activity-dependent processes addressing the central nervous system (CNS) and musculoskeletal structures are critical for maintaining motor performance. Chronic reduction in activity, whether due to a sedentary lifestyle or extended bed rest, results in impaired performance in motor tasks and thus decreased quality of life. In the first part of this paper, we give a narrative review of the effects of hypoactivity on the neuromuscular system and behavioral outcomes. Motor impairments arise from a combination of factors including altered muscle properties, impaired afferent input, and plastic changes in neural structure and function throughout the nervous system. There is a reciprocal interplay between the CNS and muscle properties, and these sensorimotor loops are essential for controlling posture and movement. As a result, patients under hypoactivity experience a self-perpetuating cycle, in with sedentarity leading to decreased motor activity and thus a progressive worsening of a situation, and finally deconditioning. Various rehabilitation strategies have been studied to slow down or reverse muscle alteration and altered motor performance. In the second part of the paper, we review representative protocols directed toward the muscle, the sensory input and/or the cerebral cortex. Improving an understanding of the loss of motor function under conditions of disuse (such as extended bed rest) as well as identifying means to slow this decline may lead to therapeutic strategies to preserve quality of life for a range of individuals. The most efficient strategies seem multifactorial, using a combination of approaches targeting different levels of the neuromuscular system., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Motor control and body representations in the central nervous system are built, i.e., patterned, during development by sensorimotor experience and somatosensory feedback/reafference. Yet, early emergence of locomotor disorders remains a matter of debate, especially in the absence of brain damage. For instance, children with developmental coordination disorders (DCD) display deficits in planning, executing and controlling movements, concomitant with deficits in executive functions. Thus, are early sensorimotor atypicalities at the origin of long-lasting abnormal development of brain anatomy and functions? We hypothesize that degraded locomotor outcomes in adulthood originate as a consequence of early atypical sensorimotor experiences that induce developmental disorganization of sensorimotor circuitry. We showed recently that postnatal sensorimotor restriction (SMR), through hind limb immobilization from birth to one month, led to enduring digitigrade locomotion with ankle-knee overextension, degraded musculoskeletal tissues (e.g., gastrocnemius atrophy), and clear signs of spinal hyperreflexia in adult rats, suggestive of spasticity; each individual disorder likely interplaying in self-perpetuating cycles. In the present study, we investigated the impact of postnatal SMR on the anatomical and functional organization of hind limb representations in the sensorimotor cortex and processes representative of maladaptive neuroplasticity. We found that 28 days of daily SMR degraded the topographical organization of somatosensory hind limb maps, reduced both somatosensory and motor map areas devoted to the hind limb representation and altered neuronal response properties in the sensorimotor cortex several weeks after the cessation of SMR. We found no neuroanatomical histopathology in hind limb sensorimotor cortex, yet increased glutamatergic neurotransmission that matched clear signs of spasticity and hyperexcitability in the adult lumbar spinal network. Thus, even in the absence of a brain insult, movement disorders and brain dysfunction can emerge as a consequence of reduced and atypical patterns of motor outputs and somatosensory feedback that induce maladaptive neuroplasticity. Our results may contribute to understanding the inception and mechanisms underlying neurodevelopmental disorders, such as DCD.

Motor control and body representation in the central nervous system (CNS) as well as musculoskeletal architecture and physiology are shaped during development by sensorimotor experience and feedback, but the emergence of locomotor disorders during maturation and their persistence over time remain a matter of debate in the absence of brain damage. By using transient immobilization of the hind limbs, we investigated the enduring impact of postnatal sensorimotor restriction (SMR) on gait and posture on treadmill, age-related changes in locomotion, musculoskeletal histopathology and Hoffmann reflex in adult rats without brain damage. SMR degrades most gait parameters and induces overextended knees and ankles, leading to digitigrade locomotion that resembles equinus. Based on variations in gait parameters, SMR appears to alter age-dependent plasticity of treadmill locomotion. SMR also leads to small but significantly decreased tibial bone length, chondromalacia, degenerative changes in the knee joint, gastrocnemius myofiber atrophy and muscle hyperreflexia, suggestive of spasticity. We showed that reduced and atypical patterns of motor outputs, and somatosensory inputs and feedback to the immature CNS, even in the absence of perinatal brain damage, play a pivotal role in the emergence of movement disorders and musculoskeletal pathologies, and in their persistence over time. Understanding how atypical sensorimotor development likely contributes to these degradations may guide effective rehabilitation treatments in children with either acquired (ie, with brain damage) or developmental (ie, without brain injury) motor disabilities., (© 2018 International Society of Neuropathology.)

In human, a chronic sensorimotor perturbation (SMP) through prolonged body immobilization alters motor task performance through a combination of peripheral and central factors. Studies performed on a rat model of SMP have shown biomolecular changes and a reorganization of sensorimotor cortex through events such as morphological modifications of dendritic spines (number, length, functionality). However, underlying mechanisms are still unclear. It is well known that phosphorylation regulates a wide field of synaptic activity leading to neuroplasticity. Another post-translational modification that interplays with phosphorylation is O-GlcNAcylation. This atypical glycosylation, reversible, and dynamic, is involved in essential cellular and physiological processes such as synaptic activity, neuronal morphogenesis, learning, and memory. We examined potential roles of phosphorylation/O-GlcNAcylation interplay in synaptic plasticity within rat sensorimotor cortex after a SMP period. For this purpose, sensorimotor cortex synaptosomes were separated by sucrose gradient, in order to isolate a subcellular compartment enriched in proteins involved in synaptic functions. A period of SMP induced plastic changes at the pre- and post-synaptic levels, characterized by a reduction in phosphorylation (synapsin1, α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptors (AMPAR) GluA2) and expression (synaptophysin, PSD-95, AMPAR GluA2) of synaptic proteins, as well as a decrease in MAPK/ERK42 activation. Expression levels of O-GlcNAc transferase/O-GlcNAcase enzymes was unchanged but we observed a specific reduction of synapsin1 O-GlcNAcylation in sensorimotor cortex synaptosomes. The synergistic regulation of synapsin1 phosphorylation/O-GlcNAcylation could affect pre-synaptic neurotransmitter release. Associated with other pre- and post-synaptic changes, synaptic efficacy could be impaired in somatosensory cortex of SMP rat. Thus, phosphorylation/O-GlcNAcylation interplay appears to be involved in synaptic plasticity by finely regulating neural activity., (© 2018 International Society for Neurochemistry.)

Intrauterine ischemia-hypoxia is detrimental to the developing brain and leads to white matter injury (WMI), encephalopathy of prematurity (EP), and often to cerebral palsy (CP), but the related pathophysiological mechanisms remain unclear. In prior studies, we used mild intrauterine hypoperfusion (MIUH) in rats to successfully reproduce the diversity of clinical signs of EP, and some CP symptoms. Briefly, MIUH led to inflammatory processes, diffuse gray and WMI, minor locomotor deficits, musculoskeletal pathologies, neuroanatomical and functional disorganization of the primary somatosensory and motor cortices, delayed sensorimotor reflexes, spontaneous hyperactivity, deficits in sensory information processing, memory and learning impairments. In the present study, we investigated the early and long-lasting mechanisms of pathophysiology that may be responsible for the various symptoms induced by MIUH. We found early hyperreflexia, spasticity and reduced expression of KCC2 (a chloride cotransporter that regulates chloride homeostasis and cell excitability). Adult MIUH rats exhibited changes in muscle contractile properties and phenotype, enduring hyperreflexia and spasticity, as well as hyperexcitability in the sensorimotor cortex. Taken together, these results show that reduced expression of KCC2, lumbar hyperreflexia, spasticity, altered properties of the soleus muscle, as well as cortical hyperexcitability may likely interplay into a self-perpetuating cycle, leading to the emergence, and persistence of neurodevelopmental disorders (NDD) in EP and CP, such as sensorimotor impairments, and probably hyperactivity, attention, and learning disorders.

Immobilization, bed rest, or sedentary lifestyle, are known to induce a profound impairment in sensorimotor performance. These alterations are due to a combination of peripheral and central factors. Previous data conducted on a rat model of disuse (hindlimb unloading, HU) have shown a profound reorganization of motor cortex and an impairment of motor performance. Recently, our interest was turned towards the role of insulin-like growth factor 1 (IGF-1) in cerebral plasticity since this growth factor is considered as the mediator of beneficial effects of exercise on the central nervous system, and its cortical level is decreased after a 14-day period of HU. In the present study, we attempted to determine whether a chronic subdural administration of IGF-1 in HU rats could prevent deleterious effects of HU on the motor cortex and on motor activity. We demonstrated that HU induces a shrinkage of hindlimb cortical representation and an increase in current threshold to elicit a movement. Administration of IGF-1 in HU rats partially reversed these changes. The functional evaluation revealed that IGF-1 prevents the decrease in spontaneous activity found in HU rats and the changes in hip kinematics during overground locomotion, but had no effect of challenged locomotion (ladder rung walking test). Taken together, these data clearly indicate the implication of IGF-1 in cortical plastic mechanisms and in behavioral alteration induced by a decreased in sensorimotor activity., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Limb immobilization or confinement to bed results in a severe atrophy and weakness of lower leg muscles. Full recovery of muscle strength and physical function is rare and may impact the patient's outcome. Studies performed on rodents have demonstrated that the deleterious structural and functional adaptations which occur during muscle deconditioning can be counteracted through adequate physiological stimuli. Thus, based on this fundamental work, we developed a device that combines mechanical stimulation of proprioceptors located in the plantar sole and Achilles' tendon. The device is adapted to patients immobilized and confined to bed. Stimulations can be applied on muscle in passive state. The protocol is non-invasive and is well accepted by patients. This paper presents the technical features of the device, as well as preliminary results of the first clinical study. This device might allow considering new therapeutic strategies for prevention of atrophy in many pathologies.

In the adult rat, sensorimotor restriction by hindlimb unloading (HU) is known to induce impairments in motor behavior as well as a disorganization of somatosensory cortex (shrinkage of the cortical representation of the hindpaw, enlargement of the cutaneous receptive fields, decreased cutaneous sensibility threshold). Recently, our team has demonstrated that IGF-1 level was decreased in the somatosensory cortex of rats submitted to a 14-day period of HU. To determine whether IGF-1 is involved in these plastic mechanisms, a chronic cortical infusion of this substance was performed by means of osmotic minipump. When administered in control rats, IGF-1 affects the size of receptive fields and the cutaneous threshold, but has no effect on the somatotopic map. In addition, when injected during the whole HU period, IGF-1 is interestingly implied in cortical changes due to hypoactivity: the shrinkage of somatotopic representation of hindlimb is prevented, whereas the enlargement of receptive fields is reduced. IGF-1 has no effect on the increase in neuronal response to peripheral stimulation. We also explored the functional consequences of IGF-1 level restoration on tactile sensory discrimination. In HU rats, the percentage of paw withdrawal after a light tactile stimulation was decreased, whereas it was similar to control level in HU-IGF-1 rats. Taken together, the data clearly indicate that IGF-1 plays a key-role in cortical plastic mechanisms and in behavioral alterations induced by a decrease in sensorimotor activity., (Copyright © 2015 Elsevier B.V. All rights reserved.)

A chronic reduction in neuromuscular activity through prolonged body immobilization in human alters motor task performance through a combination of peripheral and central factors. Studies performed in a rat model of sensorimotor restriction have shown functional and biochemical changes in sensorimotor cortex. However, the underlying mechanisms are still unclear. Interest was turned towards a possible implication of Insulin-like Growth Factor 1 (IGF-1), a growth factor known to mediate neuronal excitability and synaptic plasticity by inducing phosphorylation cascades which include the PI3K-AKT pathway. In order to better understand the influence of IGF-1 in cortical plasticity in rats submitted to a sensorimotor restriction, we analyzed the effect of hindlimb unloading on IGF-1 and its main molecular pathway in structures implied in motor control (sensorimotor cortex, striatum, cerebellum). IGF-1 level was determined by ELISA, and phosphorylation of its receptor and proteins of the PI3K-AKT pathway by immunoblot. In the sensorimotor cortex, our results indicate that HU induces a decrease in IGF-1 level; this alteration is associated to a decrease in activation of PI3K-AKT pathway. The same effect was observed in the striatum, although to a lower extent. No variation was noticed in the cerebellum. These results suggest that IGF-1 might contribute to cortical and striatal plasticity induced by a chronic sensorimotor restriction.

A sensorimotor restriction, for instance in patients confined to bed, induces an impairment in motor function, which could be due to structural and functional reorganization of the sensorimotor cortex. Hindlimb unloading (HU) is a rodent model used to reproduce the chronic weightless bearing and reduction in hindlimb movement. In this study, we determined whether a 14-day period of HU in adult rats leads to dendritic spine plasticity. For this purpose, we visualized a large number of spines on pyramidal neurons located in superficial and deep layers of the cortex within the hindpaw representation area, by means of confocal microscopy. Spines were classified according to their shape, as stubby, thin, mushroom, or filopodium. Spine density was increased (+26%) after HU. The increase concerned mainly filopodium spines (+82%) and mushrooms (+33%), whereas no change was noticed for stubby and thin spines. Spine length was decreased, whatever their shape. Head diameter evolved differently depending on the layer: it was increased in superficial layers and decreased in deeper ones. These results indicate that morphological changes accompany functional reorganization of motor cortex in response to a decrease in sensorimotor function during adulthood., (Copyright © 2013 Elsevier B.V. All rights reserved.)

A chronic reduction in neuromuscular activity through prolonged body immobilization of humans results in muscle atrophy and weakness as well as motor tasks performance impairment, which is correlated to a change in corticospinal excitability. In rats, hindlimb unloading (HU) is commonly used to mimic the effects of confinement to bed in patients. Several studies have reported changes in the representation of the somatosensory cortex in rodents submitted to HU or sensorimotor restriction by casting: remapping and enlargement of receptive fields, changes in the response of layer 4 neurons to peripheral stimulation. However, we have no data about motor cortical maps in rats submitted to a period of motor restriction during adulthood. Therefore, the objectives of the present study were twofold: to determine, in control rats and in rats submitted to a 14-day period of HU, the size and organization of hindlimb representation in the M1 cortex and to evaluate the overall excitability of M1 cortex by determining the stimulation thresholds. HU led to a dramatic decrease in the hindlimb representation on the M1 cortex (-61%, p<0.01). In addition, current thresholds for eliciting a movement were increased. The toes were less strongly affected by HU than other joint. Our main conclusion is that HU dramatically affects the organization and functioning of cortical motor maps and decreases corticospinal excitability., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Sensorimotor restriction by a 14-day period of hindlimb unloading (HU) in the adult rat induces a reorganization of topographic maps and receptive fields. However, the underlying mechanisms are still unclear. Interest was turned towards a possible implication of intracellular MAPK signaling pathway since Extracellular-signal-Regulated Kinase 1/2 (ERK1/2) is known to play a significant role in the control of synaptic plasticity. In order to better understand the mechanisms underlying cortical plasticity in adult rats submitted to a sensorimotor restriction, we analyzed the time-course of ERK1/2 activation by immunoblot and of cortical reorganization by electrophysiological recordings, on rats submitted to hindlimb unloading over four weeks. Immunohistochemistry analysis provided evidence that ERK1/2 phosphorylation was increased in layer III neurons of the somatosensory cortex. This increase was transient, and parallel to the changes in hindpaw cortical map area (layer IV). By contrast, receptive fields were progressively enlarged from 7 to 28 days of hindlimb unloading. To determine whether ERK1/2 was involved in cortical remapping, we administered a specific ERK1/2 inhibitor (PD-98059) through osmotic mini-pump in rats hindlimb unloaded for 14 days. Results demonstrate that focal inhibition of ERK1/2 pathway prevents cortical reorganization, but had no effect on receptive fields. These results suggest that ERK1/2 plays a role in the induction of cortical plasticity during hindlimb unloading.

Sensorimotor performance is highly dependent on the level of physical activity. For instance, a period of disuse induces an impairment of motor performance, which is the result of combined muscular, spinal and supraspinal mechanisms. Concerning this latter origin, our hypothesis was that intrinsic properties and input/output coupling of cells within the sensorimotor cortex might participate to the alteration in cortical motor control. The aim of the present study was thus to examine the basic electrophysiological characteristics of cortical cells in control rats and in animals submitted to 14 days of hindlimb unloading, a model of sensorimotor deprivation. Intracellular recordings were obtained in vitro from coronal slices from cortical hindpaw representation area. We have also made an attempt to determine the morphological characteristics as well as the location of the investigated neurons by biocytin labelling. Passive properties of neurons were affected by hindlimb unloading: input resistance and time constant were decreased (-20%), the rheobase was increased (+34%), whereas the resting potential was unchanged. The frequency-current relationships were also modified, the curve being shifted towards right. The size of body area of recorded neurons was unchanged in unloaded rats. Taken together, these data reflect a decrease in excitability of cortical cells in response to a decreased cortical activation., (Copyright 2010 Elsevier B.V. All rights reserved.)

During locomotion, muscles are controlled by a network of neurones located in the spinal cord and by supraspinal structures. Alterations in that neuromuscular system have a functional impact, in particular on locomotion. The hindlimb unloading (HU) model in rat has been commonly used to generate disuse since it suppresses the hindlimb loading and limits movements. In consequence, it induces plastic mechanisms in the muscle, the spinal cord and the sensorimotor cortex. The aim of this study was to assess the locomotion in HU rats in two conditions: (1) on a runway and (2) in a challenging situation involving the participation of supraspinal structures (ladder walking). For that purpose, the motor pattern has been investigated by means of 3D motion analysis of the right fore- and hindlimbs as well as electromyographic recording of the soleus and tibialis anterior muscles. The 3D motion results show that HU induces a support-dependent alteration of the kinematics: increased duration of step, stance and swing; increased ankle flexion during stance and hyperextension at toe-off; lower protraction during swing. The electromyographic results show that whatever the support, the flexor and extensor burst duration was longer in HU rats. In addition, results show that ladder exacerbates some effects of HU. As ladder walking is a situation which requires precision, it is suggested that the control of hindlimb movement by supraspinal structures is affected in HU rats.

Hindlimb unloading (HU) is known to induce changes in the neuromuscular system. However, no data describing the effects of HU on morphological characteristics of peripheral nerve have been reported so far. Therefore, we used soleus and radial nerves obtained from control and rats submitted to 14 days of HU to study the consequences of a decrease (soleus) or an increase (radial) in neural activity on its morphology. The mean number of fibers was not changed after HU. The soleus nerve axon diameter was weakly affected after HU, whereas the myelin thickness was reduced. For the radial nerve, both axon and fiber diameter were increased, and the myelin thickness and internodal distance were higher in HU rats. These results suggest that regulation of myelin maintenance undergoes plastic mechanisms. Neural activity and/or neural pattern might be essential in the maintenance of myelin sheath in adults.

The locomotor pattern, generated by the central pattern generator, is under the dependence of descending and peripheral pathways. The afferent feedback from peripheral receptors allows the animal to correct for disturbances that occur during walking, while supraspinal structures are important for locomotion in demanding situations such as ladder walking. Such walking, by regards to the control needed for accuracy of movements, is now widely used for description of consequences of nervous system dysfunction on motor performance. It is important to have a good knowledge of the changes in kinematic parameters according to walking conditions, since it might reflect different neural mechanisms. The aim of this work was to perform a 3D kinematic analysis of both hind- and forelimb during overground and ladder walking, to study qualitative and quantitative locomotor characteristics in different modes of locomotion. The analysis was performed on 5 rats. Movements of the right hind- and forelimb were evaluated using a 3D optical analyser, and EMG of the soleus and tibialis anterior muscles was synchronously recorded. Results indicate that kinematic and electromyographic characteristics of locomotion are dependent on the type of support. Changes were more obvious for hindlimb than for forelimb. Velocity, stride length and tibialis anterior burst duration were lower on ladder than on runway. In addition, during ladder walking, a protraction was noticed, rats bring their feet more rostral at the end of the swing phase. All these changes constitute an adaptive strategy to allow a better tactile activity with forelimbs and to avoid foot misplacement.

The aims of this work were to analyze the effects of a chronic (14 days) increase in the functional demand imposed on the triceps brachii and to evaluate the changes of the cortical representation of forelimb to this increased activity. The activation of triceps brachii was obtained by the hindlimb unloading (HU) model. Electromyographic activity changed from a phasic to a tonic pattern. Response amplitude increased during the first days of hyperactivity and then stabilized at an intermediate level. A transient decrease (-13% to -36% on day 2) in the mean frequency of motor units was observed. Content in myosin heavy chain of muscle fibers showed a reduction in IIb+IIx fibers in HU rats, whereas IIa+IIx fibers were more numerous. Thus, fibers tend to be more resistant to fatigue. Taken together, these observations reveal a dual plastic process. First, the nervous system reacts immediately to an environmental change, and second it reorganizes its motor command to impose a pattern of activity that is more adapted to a postural function. The extent of the cortical forelimb representation was delimited by oxidase histochemistry. No differences were detectable between control and HU animals for the period corresponding to enlarged receptive fields in the HU condition. Our observation lends support to our hypothesis that activation patterns contribute to the maintenance of neuronal properties in the somatosensory cortex. Moreover, the new tonic pattern resulting from the long contact of the paw with the floor may contribute to the adaptation of the central control of motoneuronal activity.

Environmental changes that occur in daily life or, in particular, in situations like actual or simulated microgravity require neuronal adaptation of sensory and motor functions. Such conditions can exert long-lasting disturbances on an individual's adaptive ability. Additionally, prenatal stress also leads to behavioral and physiological abnormalities in adulthood. Therefore, the aims of the present study were (a) to evaluate in adult rats the behavioral motor adaptation that follows 14 days of exposure to simulated microgravity (hindlimb unloading) and (b) to determine whether restraint prenatal stress influences this motor adaptation. For this purpose, the authors assessed rats' motor reactivity to novelty, their skilled walking on a ladder, and their swimming performance. Results showed that unloading severely impaired motor activity and skilled walking. By contrast, it had no effect on swimming performance. Moreover, results demonstrated for the first time that restraint prenatal stress exacerbates the effects of unloading. These results are consistent with the role of a steady prenatal environment in allowing an adequate development and maturation of sensorimotor systems to generate adapted responses to environmental challenges during adulthood., (Copyright (c) 2007 APA, all rights reserved.)

Hindlimb unloading is considered as a model of functional deafferentation, since in this situation the tactile information from the paw and the proprioceptive input from the limb are dramatically reduced. Unloading induces a shrinkage of the cortical representation of the affected body part associated to a reorganization of topographic maps and to an expansion of receptive fields. Previous studies have suggested that cortical plasticity was the result of a change in the balance of excitation and inhibition in the cortex. The aim of the present study was thus to determine whether deafferentation of the hindlimb representation in the somatosensory cortex, by 14 days of unloading or by surgical means (selective dorsal rhizotomy during 17 days), can change the concentration in various amino acid neurotransmitters in the deprived cortex. The present findings indicate that both types of deafferentation result in a decrease in inhibitory amino acids (GABA, taurine) without significant changes in the main excitatory amino acid (glutamate). In conclusion, the present results support the idea that cortical changes are more likely due to a release from inhibition than to an increased excitation.

We have measured by HPLC the neurotransmitter content in L(4) and L(5) spinal segmental levels in CONT rats, after 7 (HU7) and after 14 days (HU14) of hindlimb unloading. These segments are known to contain the hindlimb muscle motoneurons. The main result is the increase of two neuroexcitators (glutamate and aspartate) and two neuroinhibitors (glycine and GABA) at the L(5) spinal segmental level in HU7 group. Our data indicated that the neurotransmitter changes are restricted to spinal segmental level containing motoneurons from muscles which are strongly modified by HU condition.

This study describes the effect of simulated microgravity in rat on kinematics and electromyographic activity during treadmill locomotion. The analysis was performed in rats submitted to 14 days of hindlimb unloading (HU), in rats submitted to hindlimb unloading and then authorized to recover for 7 days (REC), and in aged-matched control rats (CON). Movements of the right hindlimb were measured with a 3D-optical analyzer (SAGA3 system) and five small infrared-reflective disks positioned on the skin, recorded by three CCD cameras. Results showed that HU rats exhibited hyperextensions at the end of the stance phase. By contrast, during the major part of the step, the ankle was less extended than CON. Possible origins of the changes are discussed. This leads to the question of how important is sensory input in the regulation of the locomotor pattern after HU. Data obtained in REC animals showed that 1 week of recovery allowed the restoration of a good locomotor performance. However, the limb motion remained abnormal, and at contrary to HU rats: higher extension during the step, except at push-off when the limb was in hyperflexion. We concluded that simulated microgravity involves a dual adaptive process: a first one during unloading, and a second one during the period of recovery, which is not a simple return to initial characteristics of the locomotor pattern.

Neurotrophins have been reported to play an important role in neuronal plasticity and to be regulated by neuronal activity and/or neurotransmitters. Recently, we have shown that hindpaw sensory restriction induces a cortical reorganisation in the hindpaw primary somatosensory cortex, and that acetylcholine plays a significant role in this process. Sensory restriction was obtained by hindlimb suspension for 14 days. In this study, we examined the effects of a long period of hindpaw sensory restriction on the NGF and BDNF mRNA and protein expressions in the hindpaw somatosensory cortex. mRNA and protein levels were assessed by RT-PCR and ELISA, respectively. First, we found that NGF and BDNF mRNA relative levels increased after hindpaw sensory restriction. Second, the level of NGF protein increased, whereas that of BDNF remained unchanged. This differential response of NGF and BDNF proteins to sensory restriction suggested different levels of gene regulation, i.e., at pretranslational or posttranslational states. Moreover, inasmuch as our results differ from other models of sensory restriction (dark rearing, whisker removal, etc.), we hypothesized that the regulation of neurotrophin expression is dependent on the type and duration of the sensory restriction. In conclusion, we argue that neuronal plasticity induced by hindpaw sensory restriction requires neurotrophin expression.

The aim of the present study was to analyse the effects of microgravity on i) the achievement of goal-directed arm movements and ii) the quadrupedal non-human primate locomotion. A reaching movement in weightlessness would require less muscle contraction since there is no need to oppose gravity. Consequently the electromyographic (EMG) activity of the monkey forelimb muscles should be changed during or after spaceflight. EMG activity of the biceps and triceps muscles during goal-directed arm movements were studied in Rhesus monkeys before, during and after 14 days of spaceflight and flight simulation at normal gravity. The EMG activity was also recorded during treadmill locomotion before and after spaceflight. When performing arm motor tasks, the delay values of the EMG bursts were unchanged during the flight. On the contrary, mean EMG was significantly decreased during the flight comparatively to the pre- and post-flight values, which were very similar. Compared with flight animals, the control ground monkey showed no change in the burst durations and mean EMG. After spaceflight, quadrupedal locomotion was modified. The animals had some difficulty in moving, and abnormal steps were numerous. The integrated area of triceps bursts was increased for the stance phase during locomotion. Taken together these data showed that spaceflight induces a dual adaptative process: first, the discharge of the motor pools of the forelimb musculature was modified during exposure to microgravity, and then upon return to Earth, monkeys changed their new motor strategy and re-adapt to normal gravity.

The aim of this study was to determine if a prolonged period (7 or 14 days) of hypodynamia-hypokinesia (HH) affects the conduction of afferent input and the cortical and spinal responsiveness. Acute recordings of cortical and spinal somatosensory evoked potentials (SEPs) were performed after stimulation of the sciatic nerve in control rats and in rats submitted to 7 or 14 days of HH. HH was obtained by unloading the hindquarter. HH induced some subtle modifications in the SEP characteristics. Latency was increased for the spinal and cortical SEPs after 7 days of HH, and restored after 14 days of HH. A decrease in the amplitude was observed after 14 days of HH for the cortical SEP only. At the end of the experiment, the compound action potential of the sciatic nerve was recorded in vitro in order to evaluate the mean conduction velocity. Results indicate that the nerve velocity was reduced after 14 days of HH. The results also suggest that sensory conduction and/or cortical and spinal excitability are changed after HH.

Hypodynamia-hypokinesia (HH) is a model of hindpaw sensory deprivation. It is obtained by unloading of the hindquarters during 14 days. In this situation, the feet are not in contact with the ground and as a consequence, the cutaneous receptors are not activated; the sensory input to the primary somatosensory cortex (SmI) is thus reduced. In a previous study, we have shown that HH induced a cortical reorganisation of the hindlimb representation. The understanding of the mechanisms involved in cortical map plasticity requires a close examination of the changes in response properties of cortical neurons during HH. The aim of the present study was thus to study the characteristics of neurons recorded from granular and infragranular layers in hindlimb representation of SmI. A total of 289 cortical neurons were recorded (158 from control rats and 131 from HH rats) in pentobarbital-anaesthetized rats. Cutaneous threshold, cutaneous receptive fields, spontaneous activity (discharge rate and instantaneous frequency) and activity evoked by air-jet stimulation (response latency and duration, amplitude) were analysed. The present study suggests that activity-dependent changes occur in the cortex. The duration of the spike waveform presented two populations of spikes: thin-spike cells (<1 ms, supposed to be inhibitory interneurons) and regular cells (>1 ms). Thin-spike cells were less frequently encountered in HH than in control rats. The analysis of regular cells revealed that after HH (1) spontaneous activity was unchanged and (2) cortical somatosensory neurons were more responsive: the cutaneous threshold was reduced and the response magnitude increased. Taken together, these results suggest a down-regulation of GABAergic function.

The effects of hypergravity (HG) on soleus and plantaris muscles were studied in Long Evans rats aged 100 days, born and reared in 2-g conditions (HG group). The morphological and contractile properties and the myosin heavy chain (MHC) content were examined in whole muscles and compared with terrestrial control (Cont) age-paired rats. The growth of HG rats was slowed compared with Cont rats. A decrease in absolute muscle weight was observed. An increase in fiber cross-sectional area/muscle wet weight was demonstrated, associated with an increase in relative maximal tension. The soleus muscle changed into a slower type both in contractile parameters and in MHC content, since HG soleus contained only the MHC I isoform. The HG plantaris muscle presented a faster contractile behavior. Moreover, the diversity of hybrid fiber types expressing multiple MHC isoforms (including MHC IIB and MHC IIX isoforms) was increased in plantaris muscle after HG. Thus the HG environment appears as an important inductor of muscular plasticity both in slow and fast muscle types.

It has been demonstrated that hypodynamia-hypokinesia (HH), a model of sensory disruption, induced a decrease in the cortical hindpaw representation and an enlargement of the cutaneous receptive fields (RFs). The present study was carried out to determine whether chronic application of atropine could prevent this reorganisation. The extent of the hindlimb representation on the somatosensory cortex was determined in control rats (C), rats submitted to HH (HH), and rats submitted to HH with a chronic cortical infusion of atropine (70 mM, HH-ATR). Our results show that the hindpaw cortical area was similar for the HH-ATR and C rats, and was smaller for the HH rats. The distribution of RFs was comparable for the C and HH-ATR groups with a high percentage of small RFs. In contrast, for the HH rats, the percentage of large RFs was higher. Atropine can thus prevent the reduction in the hindlimb cortical area induced by HH. These results suggest that cholinergic mechanisms contribute to cortical plasticity.

Hindlimb sensory deprivation is known to induce a decrease in the cortical representation of hindpaw, and an increase in the size of the cutaneous receptive fields. The aim of the present study was to determine (i) the time-course of recovery when the rat retrieves a normal use of its limbs after a 14-day period of sensory disruption and (ii) whether a 1-day period of sensory deprivation is sufficient to induce a plasticity. Our results indicate that the remodelling of the cortical map was not observed after 1 day of sensory deprivation. On the other hand, the recovery was achieved after 6 h. These findings suggest that a procedure reducing sensory function resulted in reversible changes in the somatosensory cortex. The recovery was more rapid than the induction of plasticity.

The goal of the present study was to examine the effects of chronic hindlimb unloading on fictive motor patterns which can be developed in hindlimb nerves of adult rats. The animals were divided into two groups. The first group was submitted to hindlimb unloading for 2 weeks by tail suspension. The second group served as controls. After this initial phase, the animals of both groups were acutely decorticated, paralysed and electroneurographic efferent activity was recorded from hindlimb muscle nerves under conditions of "fictive locomotion" in order to evaluate variations in central locomotor command. Fictive rhythmic motor episodes were either spontaneous or evoked by electrical stimulation of the mesencephalic locomotor region. Only the second ones were recognised as locomotor-like activities. The motor pattern was not fundamentally affected by unloading except that, after the unloading period, extensor muscle nerves were significantly more frequently activated and their burst durations were increased compared to activity in control animals, despite the fact that the phasic sensory afferent inputs were suppressed. This suggests that unloading induces plastic modifications of the central networks of neurons implicated in the locomotor command. The origin of this extensor hyperactivity is discussed. It is proposed that it could be the consequence of either changes in motoneuronal properties or of an increase in afferent input to motoneurones.

There have been many reports describing modifications of the sensory and motor cortex following various types of disuse. Hypodynamia--hypokinesia is characterized by the absence of weight-bearing and by a decrease in motor activity. We have shown a reorganization of the cortical cartography after hypodynamia--hypokinesia. In order to give an anatomical account for this cortical plasticity, we set out to determine whether cerebral and spinal structures exhibited variations of their neuronal activation. For this purpose, immunocytochemical detection of Fos protein was performed in the rat brain and spinal cord. Following stimulation of the sciatic nerve, Fos protein was detected in the primary and secondary somatosensory cortex in control rats and in rats submitted to an episode of 14 days of hypodynamia--hypokinesia. Results showed that the stimulation of the sciatic nerve induced an increase in the number of Fos-immunoreactive neurons in all these structures. Moreover, after hypodynamia--hypokinesia, the number of Fos-immunoreactive neurons was increased in the primary and secondary somatosensory cortex and in the spinal cord. These results provide evidence for a higher activation of cortical cells after hypodynamia--hypokinesia in comparison to controls. These data support the hypothesis that hypodynamia--hypokinesia contributes to the development of functional plasticity.

The main goal of this study was to identify the different fibre types of the motor units (MUs) contained in the soleus muscles from control (CONT) rats and from rats submitted to 14 days of hindlimb unloading (HU). The MU types were classified according to their contractile properties and also using glycogen depletion followed by adenosine triphosphatase (ATPase) staining. In CONT rats, the soleus muscle contained two MU types identified as slow and fast types. After HU, the MU distribution showed three populations: slow, intermediate and fast. All the MUs from HU soleus were heterogeneous in terms of fibre type composition, indicating a complex remodelling of the muscle.

The effects of clenbuterol beta(2)-agonist administration were investigated in normal and atrophied [15-day hindlimb-unloaded (HU)] rat soleus muscles. We showed that clenbuterol had a specific effect on muscle tissue, since it reduces soleus atrophy induced by HU. The study of Ca(2+) activation properties of single skinned fibers revealed that clenbuterol partly prevented the decrease in maximal tension after HU, with a preferential effect on fast-twitch fibers. Clenbuterol improved the Ca(2+) sensitivity in slow- and fast-twitch fibers by shifting the tension-pCa relationship toward lower Ca(2+) concentrations, but this effect was more marked after HU than in normal conditions. Whole muscle electrophoresis indicated slow-to-fast transitions of the myosin heavy chain isoforms for unloaded and for clenbuterol-treated soleus. The coupling of the two latter conditions did not, however, increase these phenotypical transformations. Our findings indicated that clenbuterol had an anabolic action and a beta(2)-adrenergic effect on muscle fibers and appeared to counteract some effects of unloading disuse conditions.

It is well known that both neuromuscular and perceptual properties are affected during spaceflight. These modificaitons can therefore induce dramatic alterations in the mechanical basis of movements and locomotion disturbances. The main objectives of this study were: 1) to examine whether the nervous control of muscular activity in the upper limbs of the rhesus monkey (Macaca mulatta) was modified in a microgravity environment; and 2) to quantify the electromyographic (EMG) pattern of biceps (BI) and triceps (TRI) muscles pre-, in-, and postflight during performance of goal-directed movements and locomotion.

Since the last 25 years, the cortex is considered as a dynamic entity, susceptible of changes. Various types of modifications in stimuli may lead to the plasticity of the target neurons. These include immobilisation, denervation, amputation, deafferentation... In the somatosensory system, the most important changes are a substantial reorganisation of the cortical somatotopic representation, and an enlargement of the receptive fields (RF) of cortical neurons. Hindlimb suspension (HS) is characterized by the absence of weight-bearing and a reduced motor activity. In these conditions, the cutaneous receptors located on the foot sole are deactivated. Our hypothesis is that this condition of HS can produce a reorganisation of the somatosensory cortex (SmI) and a modification in the size of the cutaneous RF.

This study was performed to determine if hypodynamia-hypokinesia (HH) could induce a reorganization of the rat somatosensory cortex. The cortical hindpaw representation was determined by stimulating the limb and recording multi-unit cortical activity. The size of the cutaneous receptive fields was also measured. After 14 days of HH, the size of the cortical hindpaw representation was decreased. The proportion of small cutaneous receptive fields decreased while the large ones increased. After 7 days of HH, no change in the two studied parameters was noticed in five animals. In the other rats, a number of sites unresponsive to cutaneous stimulation or with high thresholds was observed. This study provides evidence of a plasticity of the somatosensory cortex induced by a situation that reduces both sensory and motor functions. The cortical reorganization occurs in two stages.

Effects of hindlimb unloading on interlimb coordination were examined in adult rats walking on a treadmill at moderate speed. In the first group of animals, the electromyographic activity (EMG) of soleus muscle of both hindlimbs was recorded after 7 and 14 days of unloading. In the second group, the EMG was recorded daily until the 14th day of unloading. The general organization of locomotion was preserved in the two groups whatever the duration of the unloading. The step cycles of the two hindlimbs were always strictly alternating. However, the locomotor pattern was very irregular. A lateral instability was observed. It was accompanied by an abduction of the hindlimbs, and frequent hyperextensions of the ankle when walking. The EMG analysis showed an increase in step cycle duration and in coactivation duration of the soleus muscles (i.e. in the double stance duration). In the rats recorded daily, mean EMG was dramatically reduced the 1st day of unloading, suggesting a decrease in the neural drive. Taken together, these data indicate that 14 days of hindlimb unloading can alter the neuromuscular pattern during locomotion. It is proposed that these changes are related to changes in the peripheral sensory information.

The purpose of the study was to examine the pattern of electromyographic (EMG) activity of the rat soleus (SOL) and tibialis anterior (TA) muscles during treadmill locomotion at various speeds after 7 days of hindlimb unloading (HU). Raw EMG signals were processed to determine cycle duration, burst duration and mean EMG (burst surface divided by its duration). Cycle duration and SOL burst duration increased after HU (+7% and +5%, respectively) while TA burst duration decreased (-16%). After HU, the alternating pattern of activity between extensor and flexor muscles was maintained. Nevertheless, a co-activation of the two muscles was sometimes observed. The EMG pattern revealed no difference in the timing of the coordination between flexor and extensor muscles after HU. The delay between TA offset and SOL onset was increased (+12 ms), but this increase could be explained by the decrease in TA burst duration. Neither TA burst duration nor TA mean EMG were changed with increased treadmill speed, so that the flexor muscle activity was not related to speed of locomotion. These results would suggest that SOL activity is centrally programmed. Moreover, it is proposed that a decline in afferent feedback from SOL in rats which are suspended has an effect upon the locomotor pattern, leading to an hyperexcitability of SOL motoneurons and, via reciprocal inhibition, to a reduction in TA activity.

Electromyographic activity (EMG) was recorded from the soleus muscles of adult rats during treadmill locomotion after 7 and 14 days of hindlimb unloading, and after 7 days of recovery. Observation of the rats indicated that treadmill locomotion was disrupted after unloading since the animals had some difficulty in moving. Soleus muscle EMG analysis was performed. Onset and offset of bursts of activity were determined, and the relationships between step duration and cycle duration were analysed. Our main results were as follows: firstly, mean cycle duration was increased after 14 days of hindlimb unloading when walking at low speed. At high speed, no difference was observed. Secondly, linear regression analysis indicated that the relationships between step duration and cycle duration were altered after 7 days of unloading. Thirdly, adaptation occurred, since the normal slope and correlation coefficient were restored after 14 days of unloading. Fourthly, when speed increased, no variation of mean EMG was demonstrated after hindlimb unloading whereas an increase occurred in normal rats. Fifthly, video analysis showed that the rats presented frequent hyperextension of the hindlimb after unloading. These abnormal steps were more numerous when walking at low speed. These data would indicate that a transitory disruption of the soleus muscle motor pattern occurred after 7 days of unloading. This disruption depended on the treadmill belt speed. Possible origins of these modifications are discussed.

Cat behavioural states of attentive fixation on a target are associated with episodes of electrocortical rhythms at 40 Hz ("beta rhythms") in the parietal cortex. Previous field potential studies indicate that the nucleus posterior pars medialis of the thalamus displays this particular rhythmic activity. We investigated single units of the nucleus posterior pars medialis and its surrounding nuclei to assess their participation in the cortical beta rhythms. Only a small proportion of thalamic cells underwent changes in their firing pattern during beta episodes. "Beta-related cells" were localized in the nucleus posterior pars medialis or its immediate vicinity; no such beta-related cells were found in other regions of the lateral thalamus. Some beta-related cells showed a one-spike to one-wave relationship ("homorhythmicity"), while others displayed a prolonged decrease or a suppression of their firing throughout each beta episode ("pause cells"). For comparison, neurons in the same thalamic area were also recorded during sleep episodes with slow waves and spindles: there was no correlation between spindles and cell firing. Thus, the nucleus posterior pars medialis thalamic nucleus contains cells whose firing is correlated with the beta rhythms. No such correlation was found with sleep spindles.