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Biomedical subjects

Guy Cheron

Publications and source records attributed to Guy Cheron.

14 recordsLinked to original sources

Recognition of the physiological actions of the triphasic EMG pattern by a dynamic recurrent neural network.

Triphasic electromyographic (EMG) patterns with a sequence of activity in agonist (AG1), antagonist (ANT) and again in agonist (AG2) muscles are characteristic of ballistic movements. They have been studied in terms of rectangular pulse-width or pulse-height modulation. In order to take into account the complexity of the EMG signal within the bursts, we used a dynamic recurrent neural network (DRNN) for the identification of this pattern in subjects performing fast elbow flexion movements. Biceps and triceps EMGs were fed to all 35 fully-connected hidden units of the DRNN for mapping onto elbow angular acceleration signals. DRNN training was supervised, involving learning rule adaptations of synaptic weights and time constants of each unit. We demonstrated that the DRNN is able to perfectly reproduce the acceleration profile of the ballistic movements. Then we tested the physiological plausibility of all the networks that reached an error level below 0.001 by selectively increasing the amplitude of each burst of the triphasic pattern and evaluating the effects on the simulated accelerating profile. Nineteen percent of these simulations reproduced the physiological action classically attributed to the 3 EMG bursts: AG1 increase showed an increase of the first accelerating pulse, ANT an increase of the braking pulse and AG2 an increase of the clamping pulse. These networks also recognized the physiological function of the time interval between AG1 and ANT, reproducing the linear relationship between time interval and movement amplitude. This task-dynamics recognition has implications for the development of DRNN as diagnostic tools and prosthetic controllers.

Action Potentials↗

Targeted calretinin expression in granule cells of calretinin-null mice restores normal cerebellar functions.

Ca2 binding proteins such as calretinin, characterized by the presence of EF-hand motifs that bind Ca2+ ions, are involved in the shaping of intraneuronal Ca2+ fluxes. In the cerebellar cortex, information processing tightly relies on variations in intracellular Ca2+ concentration in Purkinje and granule cells. Calretinin-deficient (Cr-/-) mice present motor discoordination, suggesting cellular and network cerebellar dysfunctions. To determine the cell specificity of these alterations, we constructed transgenic Cr-/- mice exhibiting a selective reexpression of calretinin in granule cells through the promoter function of the GABAA receptor alpha6 subunit gene. Normal granule cell excitability and wild-type Purkinje cell firing behavior in awake mice were restored while the emergence of high-frequency oscillations was abolished. Behavioral analysis of these calretinin-rescue mice revealed that normal motor coordination was restored as compared with Cr-/- mice. These results demonstrate that calretinin is required specifically in granule cells for correct computation in the cerebellar cortex and indicate that the finetuning of granule cell excitability through regulation of Ca2+ homeostasis plays a crucial role for information coding and storage in the cerebellum.

Animals↗

Age dependence of strain determinant on mice motor coordination.

Evaluation of motor coordination and motor learning in mice remains a challenge as many factors may interact with the different tests used. Among these factors, genetic background has been reported to be a major determinant of mice performances in motor coordination tests. However, it is not known if the strain dependence of motor coordination and motor learning remains constant through life. In order to assess this point, we tested during 5 days male and female mice of three different strains (NMRI, C57BL/6J, and C57BL/6J x 129OlaHsd) in runway, rotarod, and thin rod tests at juvenile (first day of testing = postnatal day 19) and adult (3 months) age. We found a strong strain effect on motor performances and motor learning at juvenile age (C57BL/6J performing more poorly than the two other strains), whatever the tests used. Interestingly, the C57BL/6J mice were the best performing mice at the adult age. These strain rankings were observed either in male and female groups. These results demonstrate that the strain determinant on mice performances and motor learning is highly age dependent.

Aging↗

Fast oscillation in the cerebellar cortex of calcium binding protein-deficient mice: a new sensorimotor arrest rhythm.

Fast oscillations (>100 Hz) may serve physiological roles when regulated properly. They may also appear in pathological conditions. In cerebellum, 160 Hz oscillation emerge in mice lacking calbindin and/or calretinin, two proteins devoted to calcium buffering in Purkinje and granule cells, respectively. Here, we review the pharmacological and spatiotemporal properties of this fast cerebellar oscillation and the related Purkinje cell firing behaviour in alert mice. We show that this oscillation is highly synchronized along the parallel fiber beam and reversibly inhibited by gap junctions, GABA(A) and NMDA receptors blockers. Cutaneous stimulation of the whisker region transiently suppressed the oscillation which shows in some aspects similarities with cerebral "resting" rhythmic activities of wakefulness arresting to sensory or motor information such as alpha and mu rhythms. The Purkinje cells of these mutants present an increased simple spike firing rate, rhythmicity and synchronicity, and a decreased complex spike duration and subsequent pause. Both simple and complex spikes may be tightly phase-locked with the oscillation. Contrastingly, on slice recordings, the intrinsic membrane properties of Purkinje cell are similar in wild type mice and in mice lacking calbindin. The role played by this fast cerebellar oscillation in the emergence of ataxia is yet to be solved.

Animals↗

Two reference frames for visual perception in two gravity conditions.

The processing and storage of visual information concerning the orientation of objects in space is carried out in anisotropic reference frames in which all orientations are not treated equally. The perceptual anisotropies, and the implicit reference frames that they define, are evidenced by the observation of 'oblique effects' in which performance on a given perceptual task is better for horizontally and vertically oriented stimuli. The question remains how the preferred horizontal and vertical reference frames are defined. In these experiments cosmonaut subjects reproduced the remembered orientation of a visual stimulus in 1g (on the ground) and in 0g, both attached to a chair and while free-floating within the International Space Station. Results show that while the remembered orientation of a visual stimulus may be stored in a multimodal reference frame that includes gravity, an egocentric reference is sufficient to elicit the oblique effect when all gravitational and haptic cues are absent.

Analysis of Variance↗

Effect of simple spike firing mode on complex spike firing rate and waveform in cerebellar Purkinje cells in non-anesthetized mice.

Cerebellar Purkinje cells receive two different excitatory inputs from parallel and climbing fibers, causing simple and complex spikes, respectively. Purkinje cells present three modes of simple spike firing, namely tonic, silent and bursting. The influence of complex spike firing on simple spike firing has been extensively studied. However, it is unknown whether and how the simple spike firing mode may influence complex spike waveform and firing rate in vivo. We studied complex spike firing during tonic and silent mode periods in non-anesthetized mice. We found that complex spike firing rate is not influenced by simple spike firing modes, but that the complex spike waveform is altered following high frequency simple spike firing. This alteration is a specific decrement of the second depolarizing component of the complex spike. We demonstrate that the amplitude of the second depolarizing component is inversely proportional to the simple spike firing rate preceding the complex spike and that this amplitude is independent of previous complex spike firing. This waveform modulation is different from previously reported modulation in paired-pulse depression and refractoriness.

Action Potentials↗

Ventilation asymmetry after transplantation for emphysema: role of chest wall and mediastinum.

After single-lung transplantation for emphysema, the hyperinflated native lung and the graft have different extents and rates of inflation and emptying. This requires that breathing produces asymmetrical expansion of the chest wall, displacement of the mediastinum, or both. In a first study in four seated transplant recipients, we measured the volumes of the two hemithoraces with optoelectronic plethysmography. Functional residual capacity and total lung capacity were identical on the native and transplanted sides, and changes in chest wall volume during CO(2)-induced hyperpnea and FVC maneuvers were similar on both sides. Studies with computerized tomography in three of these patients and in four additional patients in supine posture indicated that the mediastinum was shifted toward the graft at functional residual capacity and total lung capacity. The mediastinum moved toward the native lung during tidal and full inspiration and toward the graft during tidal and forced expiration; additional studies with fluoroscopy showed qualitatively similar changes in upright posture. In summary, the two hemithoraces assume identical static volumes and show similar volume changes during CO(2)-induced hyperpnea and FVC maneuvers in patients with single-lung transplantation for emphysema; displacement of the mediastinum accommodates part, if not all, of the unequal lung volumes and asymmetrical ventilation.

Female↗

Inactivation of calcium-binding protein genes induces 160 Hz oscillations in the cerebellar cortex of alert mice.

Oscillations in neuronal populations may either be imposed by intrinsically oscillating pacemakers neurons or emerge from specific attributes of a distributed network of connected neurons. Calretinin and calbindin are two calcium-binding proteins involved in the shaping of intraneuronal Ca2+ fluxes. However, although their physiological function has been studied extensively at the level of a single neuron, little is known about their role at the network level. Here we found that null mutations of genes encoding calretinin or calbindin induce 160 Hz local field potential oscillations in the cerebellar cortex of alert mice. These oscillations reached maximum amplitude just beneath the Purkinje cell bodies and are reinforced in the cerebellum of mice deficient in both calretinin and calbindin. Purkinje cells fired simple spikes phase locked to the oscillations and synchronized along the parallel fiber axis. The oscillations reversibly disappeared when gap junctions or either GABA(A) or NMDA receptors were blocked. Cutaneous stimulation of the whisker region transiently suppressed the oscillations. However, the intrinsic somatic excitability of Purkinje cells recorded in slice preparation was not significantly altered in mutant mice. Functionally, these results suggest that 160 Hz oscillation emerges from a network mechanism combining synchronization of Purkinje cell assemblies through parallel fiber excitation and the network of coupled interneurons of the molecular layer. These findings demonstrate that subtle genetically induced modifications of Ca2+ homeostasis in specific neuron types can alter the observed dynamics of the global network.

Action Potentials↗

Motor strategies in standing up in children with hemiplegia.

In spastic hemiplegia, the organization of whole body movements is impaired by deficient postural control. We studied segmental motor patterns involved in standing up from supine position in 15 children with spastic hemiplegic cerebral palsy and 14 unimpaired children using a visual analysis scale previously validated for developmental research. This approach examines specific movement patterns in upper limbs, axis, and lower limbs. We found that children with hemiplegia use movement patterns described in normal children but with reduced interindividual variability and a significant preponderance of asymmetric patterns. One previously undescribed stereotyped lower limb pattern was observed in two children with spastic hemiplegia. Emergence of these patterns is consistent with the referent body image theory. This approach can systematically characterize the limited repertoire of movement in patients with disorders of movement and posture and therefore contribute to a better understanding of motor control. The approach may guide management proposals with particular reference to variability and symmetry and might be used as a follow-up tool.

Cerebral Palsy↗

From electrophysiology to chromatin: a bottom-up approach to Angelman syndrome.

Angelman syndrome is one of the most studied human diseases related to a gene that is expressed on the maternal chromosome only in at least some brain cells. It is caused by inactivation of the UBE3A gene in the brain due to various abnormalities of the 15q11-q13 chromosome inherited from the mother. It is characterized by severe developmental delay, seizures, virtual absence of speech, motor impairment, and a particular behavioral phenotype. Studies of cortical, electromyographic and cerebellar electrophysiology in patients with Angelman syndrome and a mouse model revealed unique rhythmic neurophysiological activities in the cerebral cortex, cerebellar cortex, and muscles. The oscillatory patterns may be linked to molecular pathophysiology of the syndrome involving dysregulation of synaptic neurotransmission through UBE3A-related modulation of functional GABAA receptor complexes.

Angelman Syndrome↗

Development of pendulum mechanism and kinematic coordination from the first unsupported steps in toddlers.

The inverted pendulum model in which the centre of mass of the body vaults over the stance leg in an arc represents a basic mechanism of bipedal walking. Is the pendulum mechanism innate, or is it learnt through walking experience? We studied eight toddlers (about 1 year old) at their first unsupported steps, 18 older children (1.3-13 years old), and ten adults. Two infants were also tested repeatedly over a period of 4 months before the onset of independent walking. Pendulum mechanism was quantified from the kinematics of the greater trochanter, correlation between kinetic and gravitational potential energy of the centre of body mass obtained from the force plate recordings, and percentage of recovery of mechanical energy. In toddlers, these parameters deviated significantly (P<10(-5)) from those of older children and adults, indicating that the pendulum mechanism is not implemented at the onset of unsupported locomotion. Normalising the speed with the Froude number showed that the percentage of recovery of mechanical energy in children older than 2 years was roughly similar to that of the adults (less than 5% difference), in agreement with previous results. By contrast, the percentage of recovery in toddlers was much lower (by about 50%). Pendulum-like behaviour and fixed coupling of the angular motion of the lower limb segments rapidly co-evolved toward mature values within a few months of independent walking experience. Independent walking experience acts as a functional trigger of the developmental changes, as shown by the observation that gait parameters remained unchanged until the age of the first unsupported steps, and then rapidly matured after that age. The findings suggest that the pendulum mechanism is not an inevitable mechanical consequence of a system of linked segments, but requires active neural control and an appropriate pattern of inter-segmental coordination.

Adult↗

Self-selected modular recurrent neural networks with postural and inertial subnetworks applied to complex movements.

It has been shown that dynamic recurrent neural networks are successful in identifying the complex mapping relationship between full-wave-rectified electromyographic (EMG) signals and limb trajectories during complex movements. These connectionist models include two types of adaptive parameters: the interconnection weights between the units and the time constants associated to each neuron-like unit; they are governed by continuous-time equations. Due to their internal structure, these models are particularly appropriate to solve dynamical tasks (with time-varying input and output signals). We show in this paper that the introduction of a modular organization dedicated to different aspects of the dynamical mapping including privileged communication channels can refine the architecture of these recurrent networks. We first divide the initial individual network into two communicating subnetworks. These two modules receive the same EMG signals as input but are involved in different identification tasks related to position and acceleration. We then show that the introduction of an artificial distance in the model (using a Gaussian modulation factor of weights) induces a reduced modular architecture based on a self-elimination of null synaptic weights. Moreover, this self-selected reduced model based on two subnetworks performs the identification task better than the original single network while using fewer free parameters (better learning curve and better identification quality). We also show that this modular network exhibits several features that can be considered as biologically plausible after the learning process: self-selection of a specific inhibitory communicating path between both subnetworks after the learning process, appearance of tonic and phasic neurons, and coherent distribution of the values of the time constants within each subnetwork.

Adult↗

Motor strategies in standing up in leukomalacic spastic diplegia.

In spastic diplegia impaired postural control jeopardizes the organization of whole-body movements. We studied segmental motor patterns involved in standing up from a supine position in ten children with spastic diplegia associated with periventricular leukomalacia and 14 unimpaired children using a visual analysis scale previously devised for developmental research. This approach examines specific movement patterns in upper limbs, axis and lower limbs. We found that children with spastic diplegia use movement patterns described in normal children but with markedly reduced intra- and interindividual variability. One previously undescribed stereotyped lower limb pattern was observed in four patients. This approach can systematically characterize the limited repertoire of movement in patients with spastic diplegia and therefore contribute to a better understanding of motor control.

Biomechanical Phenomena↗