Resveratrol prevents the wasting disorders of mechanical unloading by acting as a physical exercise mimetic in the rat.

Long-term spaceflight induces hypokinesia and hypodynamia, which, along microgravity per se, result in a number of significant physiological alterations, such as muscle atrophy, force reduction, insulin resistance, substrate use shift from fats to carbohydrates, and bone loss. Each of these adaptations could turn to serious health deterioration during the long-term spaceflight needed for planetary exploration. We hypothesized that resveratrol (RES), a natural polyphenol, could be used as a nutritional countermeasure to prevent muscle metabolic and bone adaptations to 15 d of rat hindlimb unloading. RES treatment maintained a net protein balance, soleus muscle mass, and soleus muscle maximal force contraction. RES also fully maintained soleus mitochondrial capacity to oxidize palmitoyl-carnitine and reversed the decrease of the glutathione vs. glutathione disulfide ratio, a biomarker of oxidative stress. At the molecular level, the protein content of Sirt-1 and COXIV in soleus muscle was also preserved. RES further protected whole-body insulin sensitivity and lipid trafficking and oxidation, and this was likely associated with the maintained expression of FAT/CD36, CPT-1, and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in muscle. Finally, chronic RES supplementation maintained the bone mineral density and strength of the femur. For the first time, we report a simple countermeasure that prevents the deleterious adaptations of the major physiological functions affected by mechanical unloading. RES could thus be envisaged as a nutritional countermeasure for spaceflight but remains to be tested in humans.

ERK is involved in the reorganization of somatosensory cortical maps in adult rats submitted to hindlimb unloading.

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.

Activity-dependent changes in the electrophysiological properties of regular spiking neurons in the sensorimotor cortex of the rat in vitro.

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.

A 3D analysis of fore- and hindlimb motion during locomotion: comparison of overground and ladder walking in rats.

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.

Effect of hindlimb suspension on activation and MHC content of triceps brachii and on the representation of forepaw on the sensorimotor cortex.

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.

Concentration of amino acid neurotransmitters in the somatosensory cortex of the rat after surgical or functional deafferentation.

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.

The structure and response properties of Golgi tendon organs in control and hypodynamia-hypokinesia rats.

The Golgi tendon organs (GTOs) are encapsulated mechano-receptors that, in normal conditions, monitor via Ib afferent fibers the contractile force. A 14-day period of hypodynamia, absence of weight bearing and hypokinesia, and reduction of motor activity (HH) is known to induce changes in postural muscles such as the soleus. At present, there is no data available regarding the Ib afferent feedback in normal rats (CONT group) and in rats after a hypodynamia-hypokinesia (HH group) period. Consequently, the aim of our study was to determine the HH effects on the morphological (histochemistry on gross morphology) and electrophysiological properties of the GTOs in rat soleus muscle. In the histological study, nine CONT and nineteen HH GTOs of the soleus muscle were identified. The results demonstrated that HH GTOs were morphologically similar to the CONT GTOs. Regarding the electrophysiological study, a L2-L6 laminectomy was performed under deep anesthesia (sodium pentobarbital, 60 mg kg(-1)). Responses in single Ib fibers from the L5 dorsal root to the isometric twitch and tetanic fused contractions of "in-series" motor units (MUs) were recorded. Twenty-three and twenty-eight GTO/MU pairs were studied in the CONT and HH groups, respectively. In the HH group, the Ib afferent response exhibited a decrease in dynamic peak for the high stimulation frequencies and an increase in static sensitivity for all stimulation frequencies. Our results suggest that after an HH period, the GTOs continue to fulfil their mechano-sensory function to signal the contractile force but with a higher static sensitivity.

Effects of a 14-day period of hindpaw sensory restriction on mRNA and protein levels of NGF and BDNF in the hindpaw primary somatosensory cortex.

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.

A 3D analysis of hindlimb motion during treadmill locomotion in rats after a 14-day episode of simulated microgravity.

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.

Hypergravity from conception to adult stage: effects on contractile properties and skeletal muscle phenotype.

This study examined the effects of an elevation of the gravity factor (hypergravity--2 g) on the molecular and functional characteristics of rat soleus and plantaris muscles. Long Evans rats were conceived, born and reared (CBR) continuously in hypergravity conditions until the age of 100 days. Whole muscle morphological parameters, Ca2+ activation characteristics from single skinned fibers, troponin (Tn) subunit and myosin heavy (MHC) and light (MLC) chains isoform compositions were examined in CBR and control muscles from age-paired terrestrial rats. Decreases in body and muscle mass in soleus and plantaris muscles were observed and associated, in the soleus, with a decrease in fiber diameter. The specific force of CBR soleus fibers was increased, and correlated with the elevation of Ca2+ affinity. This was accompanied by slow-to-slower TnC and TnI isoform transitions and a rearrangement in TnT fast isoform content. The MHC transformations of the soleus after hypergravity were associated with the up (down)-regulation of the MHCI (MHCIIa) mRNA isoforms. The MLC2 phosphorylation state remained unchanged in the soleus muscle. The results suggested that the gravity factor could interact with rat muscle development and that hypergravity experiments could provide good tools for the study of myofibrillar protein plasticity and their associated pathways of regulation.

Effects of unilateral and bilateral labyrinthectomy on rat postural muscle properties: the soleus.

The aim of our study was to determine whether the suppression of the vestibular inputs could have effects on the soleus muscle properties similar to the modifications observed after an episode of microgravity. The inner ear lesion was performed by surgical labyrinthectomy. Twenty-nine male Wistar rats were used for this study and were divided into three experimental groups: control (CONT, n=7), unilateral labyrinthectomized (UL, n=14) and bilateral labyrinthectomized (BL, n=8). Mechanical, histochemical and electrophoretic parameters were determined 17 days after the operation. Furthermore, electromyographic (EMG) activity of the soleus muscle was examined at 1 h, 1 day and 17 days. Our results showed that UL and BL groups did not present any sign of muscle atrophy when compared to CONT group. However, the contractile and phenotypical characteristics of UL and BL soleus muscles revealed that the muscle evolved from slow toward a slower type. This transition was correlated with a more tonic EMG activity pattern. To conclude, our data demonstrated that soleus muscle transformations observed after microgravity (muscle atrophy, slow-to-fast transition, phasic EMG activity) were not directly the consequence of a vestibular silence.

Expression of Myosin heavy chain isoforms in rat soleus muscle spindles after 19 days of hypergravity.

The aim of this study was to determine whether a period of 19 days in hypergravity was long enough to induce changes in the expression of myosin heavy chain (MyHC) isoforms in the muscle spindles. The soleus muscle of 10 male Wistar rats (control: CONT, n=5; hypergravity: HG, n=5) was frozen, cut into serial sections, and labeled with antibodies against MyHCs: I, IIA, IIA + IIX + IIB, slow-tonic, and alpha-cardiac. Forty CONT and 45 HG spindles were analyzed. The results from HG spindles compared to CONT showed that there was no change in the cross-sectional area of intrafusal fibers. However, along the entire length of B1 fibers, the expression of both MyHC I and alpha-cardiac was increased significantly, whereas the labeling against MyHC IIA and MyHC slow-tonic was decreased. In B2 fibers, the labeling against MyHC IIA (region A), slow-tonic (region A), and fast myosins (regions A-C) was statistically decreased. In chain fibers, the labeling against both MyHC IIA and fast MyHC was reduced significantly. We conclude that hypergravity has a real impact on the MyHC content in the muscle spindles and induces some inverse changes of those observed in hypogravity for MyHCs I, alpha-cardiac, and slow-tonic.

Effects of hypodynamia-hypokinesia on somatosensory evoked potentials in the rat.

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.

p53 inactivation leads to impaired motor synchronization in mice.

We have combined genetic and pharmacological approaches to investigate the behavioural consequences of inactivation of the murine p53 protein. Our behavioural analysis revealed that p53-null mice (p53KO) exhibit a very specific and significant motor deficit in rapid walking synchronization. This deficit, observed using the rotarod test, was the only behavioural defect of p53KO mice. We demonstrated that it was not due to an increase in neuronal number or abnormal connectivity in the olivo-cerebellar system, thought to control motor synchronization. In order to test the role of p53 in the central nervous system, we injected a pharmacological inhibitor of p53 activation, pifithrin-alpha, into the cerebellum of wild-type mice. This treatment mimicked the walking synchronization deficit of p53KO mice, suggesting that presence of p53 protein in the cerebellum is necessary to execute this synchronization of walking. Our investigation reveals a functional role of cerebellar p53 protein in adult walking synchronization.

Compared effects of hindlimb unloading versus terrestrial deafferentation on muscular properties of the rat soleus.

Hindlimb unloading is known to induce some neuromuscular changes especially in postural muscles such as the soleus. Our goal was to determine the role of proprioceptive inputs on these modifications by comparing soleus muscle properties of rats being either hindlimb unloaded or terrestrial deafferented. Under deep anesthesia, a first group of rats were submitted to a bilateral deafferentation (DEAF group, n = 6) performed by section of the dorsal roots L(3) to L(5) after laminectomy. A second group of rats was submitted to a hindlimb-unloading period (HU group, n = 6). After 14 days, the morphological and contractile properties as well as the content in myosin heavy-chain (MHC) isoforms were studied in the right soleus muscle in HU and DEAF groups. The results were compared to those obtained in control animals (CON group). After HU versus CON group, the soleus muscle was atrophied and presented a decrease in muscle forces in relation with a slow-to-fast transition characterized by a decrease in kinetic contractile parameters and by an overexpression in the fast MHC isoforms. The DEAF soleus muscle showed both a significant muscle atrophy and a loss of forces when compared with CON rats. The comparison between DEAF and HU rats indicated that some modifications occurring after HU are purely of motor origin (i.e., slow to fast transition), whereas muscle atrophy and decrease in muscle force are partly the result of an afferent silent. Our study underlined the importance of afferent input integrity in the maintenance of muscle characteristics.

Effects of hypodynamia-hypokinesia on the muscle spindle discharges of rat soleus muscle.

The aim of this study was to determine whether Ia and II fiber discharges of soleus muscle spindles were modified after a 14-day period of hypodynamia (absence of weight bearing) and hypokinesia (reduction of motor activity). Fifty-one and 38 afferent fibers were studied, respectively, in control and hypodynamia-hypokinesia (HH) groups. Under deep anesthesia (pentobarbital, 30 mg/kg), a L3-L6 laminectomy was performed. Unitary potentials from the L5 dorsal root were recorded in response to ramp-and-hold stretches applied at two stretch amplitudes (3 and 4 mm) and four stretch velocities (6, 10, 15, and 30 mm/s) and to sinusoidal stretches applied at four stretch amplitudes (0.12, 0.25, 0.5, and 1 mm) and six stretch frequencies (0.5, 1, 2, 3, 6, and 10 Hz). In both animal groups, the Ia fibers showed higher dynamic index values, smaller linear range, and higher vibration sensitivity than the II fibers. They also exhibited a pause in their discharges during the stretch release contrary to II fibers, which displayed no pause in their responses. After HH, our results showed that for both fiber types all parameters measured under ramp-and-hold stretches (except the static sensitivity) were significantly increased and under sinusoidal stretches, the vibration sensitivity increased, and the response amplitude only increased at 0.12-mm stretch amplitude. The linear range of Ia afferents was limited to 0.12 mm, whereas it was unchanged for the II fibers. After HH, the stretches could be better transmitted to the muscle spindles, probably resulting from changes in passive mechanical properties of the soleus.

Contractile properties of rat single muscle fibers and myosin and troponin isoform expression after hypergravity.

The effects of 19 days of hypergravity (HG) were investigated on the biochemical and physiological properties of the slow soleus muscle and its fast agonist, the plantaris. HG was induced by rotational centrifugation that led to a 2-G gravity level. The HG rats were characterized by a slower body growth than control, whereas the soleus muscle mass was increased by 15%. Using electrophoretic techniques, we showed that the distribution of myosin heavy chain and troponin T isoforms was not modified after HG in both soleus and plantaris. In contrast, the isoform expression pattern of two troponin subunits, troponin I and troponin C, was changed in a slow-to-fast manner only in the soleus. From tension-pCa relationships, changes in Ca(2+) activation threshold by 0.18 pCa unit indicated a decrease in Ca(2+) sensitivity and an increase in the slope of the curve, attesting to a higher cooperativity along the thin filament after HG. Comparison of our HG data with previous results in microgravity conditions indicated that muscle characteristics, except muscle mass, did not evolve linearly from 0 to 2 G.

Characterization of spindle afferents in rat soleus muscle using ramp-and-hold and sinusoidal stretches.

The discharge properties of 51 afferents were studied in the rat soleus muscle spindles. Under deep anesthesia using a pentobarbital sodium solution (30 mg/kg), a laminectomy was performed and the right L(4) and L(5) dorsal and ventral roots were transected near their entry into the spinal cord. In situ, the minimal (L(min)) muscle length [3 +/- 0.08 (SE) cm] of the soleus was measured at full ankle extension. Unitary potentials from the L(5) dorsal root were recorded in response to ramp-and-hold stretches applied at 3 mm (S3) and 4 mm (S4) amplitudes and four stretch velocities (6, 10, 15, and 30 mm/s), sinusoidal stretches performed at four amplitudes (0.12, 0.25, 0.5, and 1 mm) and six stretch frequencies (0.5, 1, 2, 3, 6, and 10 Hz), and vibrations applied at 50-, 100-, and 150-Hz frequencies. These two kinds of stretches were performed at three different muscle lengths (L(min+10%), L(min+15%), and L(min+20%)), whereas vibrations were applied at L(min+20%) muscle length. Conduction velocity of the fibers was calculated but did not allow to discriminate different fiber types. However, the mean conduction velocity of the first fiber group (43.3 +/- 0.8 m/s) was significantly higher than that of the second fiber group (33.9 +/- 0.9 m/s). Three parameters allowed to differentiate the responses of primary and secondary endings: the dynamic index (DI), the discharge during the stretch release from the ramp-and-hold stretches, and the linear range and the vibration sensitivity from sinusoidal stretches. The slope histogram of the linear regression based on the DI and the stretch velocity was clearly bimodal. Therefore the responses were separated into two groups. During the stretch release at a velocity of 3 mm/s, the first response group (n = 26) exhibited a pause, whereas the second (n = 25) did not. The linear range of the second ending group (0.12-1 mm) was broader than that of the first (0.12-0.25 mm). The first ending group showed a higher sensitivity to high-vibration frequencies of small amplitude than the second. In comparison with the literature, we can assert that the first and the second ending groups corresponded to the primary and secondary endings, respectively. In conclusion, our study showed that in rat soleus muscle spindles, it was possible to immediately classify the discharge of Ia and II fibers by using some parameters measured under ramp-and-hold and sinusoidal stretches.

Electromyographic activity in the Rhesus monkey forelimb muscles during a goal directed movement and locomotion before, during and after spaceflight.

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.

Atropine prevents the changes in the hindlimb cortical area induced by hypodynamia-hypokinesia.

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.