Consequences of an atypical postnatal sensorimotor experience on locomotor development in rats

De nombreuses études ont montré qu’une expérience sensorimotrice atypique peut entrainer des altérations des sorties motrices ainsi que des déficits périphériques et centraux. Ces modifications peuvent survenir à des âges où les réseaux sont matures, mais pourraient être encore plus importantes lorsqu’ils sont immatures. Cependant, la grande majorité de ces études a été réalisée chez le rongeur adulte. A la naissance, les réseaux spinaux impliqués dans le comportement locomoteur ne sont pas tous matures. De nombreux processus de maturation postnataux se mettent en place durant les premières semaines chez le rat. Des études récentes, utilisant un modèle d’immobilisation des pattes arrière chez le rat, suggèrent qu’une expérience sensorimotrice atypique vécue durant cette période critique entraîne des altérations bien plus sévères et persistantes chez l’animal adulte. Dans cette thèse, nous avons approfondi cette caractérisation du modèle tardif ayant vécu une immobilisation postnatale des pattes arrière. Par la suite, nous avons étudié les conséquences précoces de cette immobilisation postnatale chez le rat. En combinant des approches électrophysiologiques et comportementales, nous avons mis en évidence des différences phénotypiques précoces importantes. Celles-ci ne semblent pas être dues à des modifications centrales et pourraient être le reflet d’altérations périphériques. Nous avons également mis en évidence des déficits importants du comportement locomoteur précoce. L’ensemble de ce travail suggère qu’une expérience sensorimotrice atypique vécue durant la période postnatale peut conduire à des modifications développementales précoces des réseaux moteurs spinaux.Many studies have shown that atypical sensorimotor experience can lead to alterations in motor output as well as peripheral and central deficits. These changes can occur at ages when the networks are mature, but may be even more important when they are immature. However, the vast majority of these studies have been conducted in the adult rodent. At birth, not all spinal networks involved in locomotor behaviour are mature. Many postnatal maturation processes take place during the first weeks of life in the rat. Recent studies using a rat hindlimb immobilisation model suggest that atypical sensorimotor experience during this critical period results in much more severe and persistent alterations in the adult animal. In this thesis, we further characterized the late model with postnatal hindlimb immobilization. Subsequently, we investigated the early consequences of this postnatal immobilisation in the rat. Using a combination of electrophysiological and behavioural approaches, we found significant early phenotypic differences. These do not appear to be due to central changes and may reflect peripheral alterations. We also found significant deficits in early locomotor behaviour. Taken together, this work suggests that atypical sensorimotor experience in the postnatal period may lead to early developmental changes in spinal motor networks

Sonic Hedgehog Signaling Agonist (SAG) Triggers BDNF Secretion and Promotes the Maturation of GABAergic Networks in the Postnatal Rat Hippocampus

International audienceSonic hedgehog (Shh) signaling plays critical roles during early central nervous system development, such as neural cell proliferation, patterning of the neural tube and neuronal differentiation. While Shh signaling is still present in the postnatal brain, the roles it may play are, however, largely unknown. In particular, Shh signaling components are found at the synaptic junction in the maturing hippocampus during the first two postnatal weeks. This period is characterized by the presence of ongoing spontaneous synaptic activity at the cellular and network levels thought to play important roles in the onset of neuronal circuit formation and synaptic plasticity. Here, we demonstrate that non-canonical Shh signaling increases the frequency of the synchronized electrical activity called Giant Depolarizing Potentials (GDP) and enhances spontaneous GABA post-synaptic currents in the rodent hippocampus during the early postnatal period. This effect is mediated specifically through the Shh co-receptor Smoothened via intracellular Ca 2+ signal and the activation of the BDNF-TrkB signaling pathway. Given the importance of these spontaneous events on neuronal network maturation and refinement, this study opens new perspectives for Shh signaling on the control of early stages of postnatal brain maturation and physiology

From cerebral palsy to developmental coordination disorder: Development of preclinical rat models corresponding to recent epidemiological changes

International audienceThe most common physical disability in children, cerebral palsy 22 (CP), involves a group of disorder of movement and posture and of 23 motor function, including spasticity (85-91% of cases) and is 24 caused by a lesion, interference or abnormality that originates i