Research reportKinematics of treadmill locomotion in mice raised in hypergravity
Highlights
► The adaptation of the motor system to gravity involves several critical periods. ► Exposition to hypergravity before the acquisition of locomotion modifies the posture. ► Exposition to hypergravity only during the acquisition of locomotion changes the gait.
Introduction
Altricial rodent species like the rats and the mice show an immature motor control at birth [1]. Basic motor structures, like scapular and pelvic central pattern generators are functional [2] and many of the adult skeletal configurations are already present at birth [3], but the motor system matures slowly over the first postnatal weeks, and the pups do not walk spontaneously before the end of second week of life [1], [4]. The development of locomotion fits the stages of neuroanatomical changes [5], [6], but neither the force production by muscles nor the neuromuscular innervation patterns nor the maturational aspects of motoneurones alone explain the postponed development [7]. Indeed, walking patterns can be induced early after birth with an appropriate stimulation [8]. Probably the high survival value of maintaining the pups in the safe nest area contributes to silencing motor activity [9], but the immaturity of underlying systems is a strong limiting factor in the motor output, and the slow development of postural control is the main limiting factor for the adult type of locomotion to occur [6], [10].
The gravitational environment perceived during the postnatal development provides the frame reference for movements and mechanically constraints the musculo-skeletal system. It is suspected to regulate the fine tuning of motoneurones, and the adjustment the vestibulo-motor connections in charge of postural control. In agreement with this proposition, some pieces of evidence suggest that the motor control is tuned by the environmental constraints experienced during the output of early motor activities. For instance, the development of motononeural dendritic bundles [11], the maturation of neuromuscular connections [7], [12], the orientation of slow/fat muscle typology [13], and the final maturation of muscles spindles [14] occur over the same time course as independent locomotion.
A pertinent paradigm to investigate the role of postural control in the acquisition of locomotion consists in altering the gravity level during the motor development. Changing the gravity level during delimited periods of time is susceptible to orient differently the maturation of the motor control, depending on the state of development of the various underlying structures. Previous studies on rats showed that the exposition to microgravity [16], [17] or hypergravity [18] during different periods of the postnatal development had different consequences, and led to permanent changes in the kinematics walking and swimming [16], [17]. The persistent motor changes reported in rats that developed in altered gravity confirmed the key role of the gravity during the motor development and supposed the existence of critical periods in the motor development of rats [16].
The present study aimed at exploring the long term effects of the early exposition to hypergravity during periods of the mice development encompassing main parts of either the vestibular or the motor development or both. The vestibular organ develops in utero from embryological day 12 (E12), and maturation of epithelia is almost achieved during the second week of life [15] even though morphological changes continues until the age of 1 month, in relation with the postural adaptation to quadruped locomotion. The development of motor functions starts also in utero, but major developmental stages appear between postnatal day 13 (P13) and P30. The experimental groups consisted of mice centrifuged from conception to P10, from P10 to P30 or from conception to P30. The kinematic analysis of movement and skeletal geometry was studied by means of the videoradiography of the skeleton during sequences of locomotion on a motorized treadmill. The results showed differential consequences on the posture and gait depending on the period of early exposition to hypergravity and confirmed the existence of critical periods in the motor development of mice. These results are discussed in relation with the development of motor and vestibular functions.
Section snippets
Animals
The neonate mice used in the present study were issued from pairs of C57Bl/6j mice provided by Charles River France (Les Oncins, 69210 St Germain Sur L’arbesle), and housed locally until the experimental sessions. We used only multiparous females to reduce the risks of misbehaving with the pups [19], and the adult mice were centrifuged at a level of 2G for at least 8 weeks before the experiments, to habituate them to the centrifugation and reduce the stress during the experimental phase. The
Gait parameters with treadmill speed fixed to 33 cm s−1
The experimental series consisted of a total of 420 cycles. The 2way ANOVAs revealed a significant gender effect in almost all the kinematic parameters (Table 1). The females walked with a smaller stride length and a higher stride frequency than males. They showed also an increased forelimb DF, and a larger phase lag, but the tests did not show any group × gender interaction, thus males and females were grouped in the analyses.
All the kinematic parameters showed a significant group effect (Table 1
General considerations
The present study provided the first accurate measure of the kinematics of locomotion of mice walking on a treadmill. The spatial accuracy was obtained by measuring the actual movements of bones with videoradiography, and the temporal accuracy was provided by the high speed of video recording (with a sampling of one image every 4 ms). Owing to these techniques, the measure of angles excursion was more precise than in the previous mice studies using markers fixed on the skin [34], particularly
Acknowledgements
This study was supported by grants from the French National Space Agency (CNES) (Program ‘Microgravity and Development’) and from the ‘Agence nationale de la Recherche’ ANR-09-BLAN-0148 (AdapHyG). M. Bojados had a fellowship from CNES and the regional PACA
References (50)
- et al.
Postnatal development of locomotion in the laboratory rat
Animal Behaviour
(1975) - et al.
Early olfactory-induced rhythmic limb activity in the newborn rat
Developmental Brain Research
(1998) - et al.
Postural development in rats
Experimental Neurology
(2006) - et al.
The development of skilled walking in the rat
Behavioural Brain Research
(2009) Posture and locomotion in the rat: independent or interdependent development?
Neuroscience & Biobehavioral Review
(1998)The final common pathway in postural control – developmental perspective
Neuroscience & Biobehavioral Review
(1998)The early development of motor control in neonate rat
Comptes Rendus Palevol
(2006)- et al.
Role of gravity in the development of posture and locomotion in the neonatal rat
Brain Research Reviews
(1998) - et al.
Development of short latency vestibular evoked potentials in the neonatal rat
Hearing Research
(1999) - et al.
Identification of a critical period for motor development in neonatal rats
Neuroscience
(1992)
Exposure to altered gravity during specific developmental periods differentially affects growth, development, the cerebellum and motor functions in male and female rats
Advances in Space Research
Bird terrestrial locomotion as revealed by 3D kinematics
Zoology
The adaptation of limb kinematics to increasing walking speeds in freely moving mice 129/Sv and C57BL/6
Behavioural Brain Research
Gait analysis in the mouse
Physiology & Behavior
How does a mouse increase its velocity?. A model for investigation in the control of locomotion
Comptes Rendus Palevol
A 3D analysis of hindlimb motion during treadmill locomotion in rats after a 14-day episode of simulated microgravity
Behavioural Brain Research
Contribution of cutaneous inputs from the hindpaw to the control of locomotion in rats
Behavioural Brain Research
Effect of skin movement on the analysis of hindlimb kinematics during treadmill locomotion in rats
Journal of Neuroscience Methods
A comparison of two-dimensional and three-dimensional techniques for the determination of hindlimb kinematics during treadmill locomotion in rats following spinal cord injury
Journal of Neuroscience Methods
Gait parameters of treadmill versus overground locomotion in mouse
Behavioural Brain Research
Kinematics of treadmill locomotion in rats conceived, born, and reared in a hypergravity field (2 g). Adaptation to 1 g
Behavioural Brain Research
Adaptive transformation of rat soleus motor units during growth
Journal of Neurological Science
Development and consistency of gait in the mouse
Physiological Behaviour
The postnatal development of behavioral states in the rat
Developmental Psychobiology
Early walking in the neonatal rat: a kinematic study
Behavioral Neuroscience
Cited by (20)
Centrifugation and hypergravity in the bone
2019, Encyclopedia of Biomedical EngineeringBehavioral outcome measures to improve experimental stroke research
2018, Behavioural Brain ResearchCitation Excerpt :Detailed analyses of mouse and rat locomotion have been described in the literature [91–93]. In a few studies, the effects of various external conditions and biological variables ranging from age to hypergravity have also been analyzed [94,95]. In malonate-induced lesions of the dorsal striatum, 3D motion capture technology was used to assess treadmill running kinematics in rats with and without obstacles.
Intermittent application of hypergravity by centrifugation attenuates disruption of rat gait induced by 2 weeks of simulated microgravity
2015, Behavioural Brain ResearchCitation Excerpt :Although each recording session involved several trials until the animal performed successive gait, each bout lasted <10 s, and breaks for the subject were introduced to avoid fatigue. For subsequent analysis, a total of 10 steps for each animal were obtained from portions of sequences in which the animal walked at an uniform velocity for at least 5 consecutive steps [22]. To ensure data accuracy, the precise coordinates were calibrated by recording a cube of known size (5 × 20 × 10 cm [x × y × z]) before each session.
Development of Vestibular Systems in Altered Gravity
2014, Development of Auditory and Vestibular Systems: Fourth EditionFunctional Development of the Vestibular System: Sensorimotor Pathways for Stabilization of Gaze and Posture
2014, Development of Auditory and Vestibular Systems: Fourth Edition