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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.)

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.)

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.)

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 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.)

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.)

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.

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.

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.

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.

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.

Previous data have suggested that in the cat, expectancy behaviour (waiting for a target to appear) and associated electrocortical, focal, synchronized activity ('mu' rhythms) are modulated by a noradrenergic system possibly originating from the locus coeruleus (LC). To test the latter hypothesis, we have examined the behavioural and ECoG changes induced after bilateral LC lesions. Our results demonstrated that destruction of the anterior 3/4th of the LC (A6 noradrenergic cell group) resulted in a considerable increase of mu rhythms and expectancy behaviour, without episodes of drowsiness that normally occur. Destruction of the posterior fourth of LC (A4 noradrenergic group) only increased the duration of slow sleep. Extending the A6 lesion to include the dorsal ascending noradrenergic bundle also increased the expectancy behaviour and mu rhythms. Finally, when the nucleus subcoeruleus was also involved, the duration of slow sleep and the frequency of paradoxical sleep episodes increased. These findings indicate that the LC exerts an inhibitory effect on structures involved in the induction and persistence of expectancy behaviour with accompanying mu rhythms.