Cholinergic Partition Cells and Lamina X Neurons Induce a Muscarinic-Dependent Short-Term Potentiation of Commissural Glutamatergic Inputs in Lumbar Motoneurons

Acetylcholine and the activation of muscarinic receptors influence the activity of neural networks generating locomotor behavior in the mammalian spinal cord. Using electrical stimulations of the ventral commissure, we show that commissural muscarinic (CM) depolarizations could be induced in lumbar motoneurons. We provide a detailed electrophysiological characterization of the muscarinic receptors and the membrane conductance involved in these responses. Activation of the CM terminals, originating from lamina X neurons and partition cells, induced a pathway-specific short-term potentiation (STP) of commissural glutamatergic inputs in motoneurons. This STP is occluded in the presence of the muscarinic antagonist atropine. During fictive locomotion, the activation of the commissural pathways transiently enhanced the motor output in a muscarinic-dependent manner. This study describes for the first time a novel regulatory mechanism of synaptic strength in spinal locomotor networks. Such cellular mechanisms would endow the locomotor central pattern generators with adaptive processes needed to generate appropriate synaptic inputs to motoneurons during different motor tasks

Left-Right Facial Orientation of Familiar Faces: Developmental Aspects of « the Mere Exposure Hypothesis »

We investigated the developmental aspect of sensitivity to the orientation of familiar faces by asking 38 adults and 72 children from 3 to 12 years old to make a preference choice between standard and mirror images of themselves and of familiar faces, presented side-by-side or successively. When familiar (parental) faces were presented simultaneously, 3- to 5-year-olds showed no preference, but by age 5–7 years an adult-like preference for the standard image emerged. Similarly, the adult-like preference for the mirror image of their own face emerged by 5–7 years of age. When familiar or self faces were presented successively, 3- to 7-year-olds showed no preference, and adult-like preference for the standard image emerged by age 7–12 years. These results suggest the occurrence of a developmental process in the perception of familiar face asymmetries which is retained in memory related to knowledge about faces

Comparison of Trunk Activity during Gait Initiation and Walking in Humans

To understand the role of trunk muscles in maintenance of dynamic postural equilibrium we investigate trunk movements during gait initiation and walking, performing trunk kinematics analysis, Erector spinae muscle (ES) recordings and dynamic analysis. ES muscle expressed a metachronal descending pattern of activity during walking and gait initiation. In the frontal and horizontal planes, lateroflexion and rotation occur before in the upper trunk and after in the lower trunk. Comparison of ES muscle EMGs and trunk kinematics showed that trunk muscle activity precedes corresponding kinematics activity, indicating that the ES drive trunk movement during locomotion and thereby allowing a better pelvis mobilization. EMG data showed that ES activity anticipates propulsive phases in walking with a repetitive pattern, suggesting a programmed control by a central pattern generator. Our findings also suggest that the programs for gait initiation and walking overlap with the latter beginning before the first has ended

Serotonergic modulation of sacral dorsal root stimulation-induced locomotor output in newborn rat

International audienceDescending neuromodulators from the brainstem play a major role in the development and regulation of spinal sensorimotor functions. Here, the contribution of serotonergic signaling in the lumbar spinal cord was investigated in the context of the generation of locomotor activity. Experiments were performed on in vitro spinal cord preparations from newborn rats (0–5 days). Rhythmic locomotor episodes (fictive locomotion) triggered by tonic electrical stimulations (2Hz, 30s) of a single sacral dorsal root were recorded from bilateral flexor-dominated (L2) and extensor-dominated (L5) ventral roots. We found that the activity pattern induced by sacral stimulation evolves over the 5 post-natal (P) day period. Although alternating rhythmic flexor-like motor bursts were expressed at all ages, the locomotor pattern of extensor-like bursting was progressively lost from P1 to P5. At later stages, serotonin (5-HT) and quipazine (5-HT2A receptor agonist) at concentrations sub-threshold for direct locomotor network activation promoted sacral stimulation-induced fictive locomotion. The 5-HT2A receptor antagonist ketanserin could reverse the agonist's action but was ineffective when fictive locomotion was already expressed in the absence of 5-HT (mainly before P2). Although inhibiting 5-HT7 receptors with SB266990 did not affect locomotor pattern organization, activating 5-HT1A receptors with 8-OH-DPAT specifically deteriorated extensor phase motor burst activity. We conclude that during the first 5 post-natal days in rat, serotonergic signaling in the lumbar cord becomes increasingly critical for the expression of fictive locomotion. Our findings therefore further underline the importance of both descending serotonergic and sensory afferent pathways in shaping locomotor activity during postnatal development

Noradrenergic Modulation of Intrinsic and Synaptic Properties of Lumbar Motoneurons in the Neonatal Rat Spinal Cord

Although it is known that noradrenaline (NA) powerfully controls spinal motor networks, few data are available regarding the noradrenergic (NAergic) modulation of intrinsic and synaptic properties of neurons in motor networks. Our work explores the cellular basis of NAergic modulation in the rat motor spinal cord. We first show that lumbar motoneurons express the three classes of adrenergic receptors at birth. Using patch-clamp recordings in the newborn rat spinal cord preparation, we characterized the effects of NA and of specific agonists of the three classes of adrenoreceptors on motoneuron membrane properties. NA increases the motoneuron excitability partly via the inhibition of a KIR like current. Methoxamine (α1), clonidine (α2) and isoproterenol (β) differentially modulate the motoneuron membrane potential but also increase motoneuron excitability, these effects being respectively inhibited by the antagonists prazosin (α1), yohimbine (α2) and propranolol (β). We show that the glutamatergic synaptic drive arising from the T13-L2 network is enhanced in motoneurons by NA, methoxamine and isoproterenol. On the other hand, NA, isoproterenol and clonidine inhibit both the frequency and amplitude of miniature glutamatergic EPSCs while methoxamine increases their frequency. The T13-L2 synaptic drive is thereby differentially modulated from the other glutamatergic synapses converging onto motoneurons and enhanced by presynaptic α1 and β receptor activation. Our data thus show that the NAergic system exerts a powerful and complex neuromodulation of lumbar motor networks in the neonatal rat spinal cord

Brainstem Steering of Locomotor Activity in the Newborn Rat

International audienceControl of locomotion relies on motor loops conveying modulatory signals between brainstem and spinal motor circuits. We investigated the steering control of the brainstem reticular formation over the spinal locomotor networks using isolated brainstem-spinal cord preparations of male and female neonatal rats. First, we performed patch-clamp recordings of identified reticulospinal cells during episodes of fictive locomotion. This revealed that a spinal ascending phasic modulation of reticulospinal cell activity is already present at birth. Half of the cells exhibited tonic firing during locomotion, while the other half emitted phasic discharges of action potentials phase locked to ongoing activity. We next showed that mimicking the phasic activity of reticulospinal neurons by applying patterned electrical stimulation bilaterally at the ventral caudal medulla level triggered fictive locomotion efficiently. Moreover, the brainstem stimuli-induced locomotor rhythm was entrained in a one-to-one coupling over a range of cycle periods (2-6 s). Additionally, we induced turning like motor outputs by either increasing or decreasing the relative duration of the stimulation trains on one side of the brainstem compared to the other. The ability of the patterned descending command to control the locomotor output depended on the functional integrity of ventral reticulospinal pathways and the involvement of local spinal central pattern generator circuitry. Altogether, this study provides a mechanism by which brainstem reticulospinal neurons relay steering and speed commands to the spinal locomotor networks

Sustained Gq-Protein Signaling Disrupts Striatal Circuits via JNK

International audienceThe dorsal striatum is a major input structure of the basal ganglia and plays a key role in the control of vital processes such as motor behavior, cognition, and motivation. The functionality of striatal neurons is tightly controlled by various metabotropic receptors. Whereas the G s /G i-protein-dependent tuning of striatal neurons is fairly well known, the precise impact and underlying mechanism of G q-protein-dependent signals remain poorly understood. Here, using different experimental approaches, especially designer receptor exclusively activated by designer drug (DREADD) chemogenetic technology, we found that sustained activation of G q-protein signaling impairs the functionality of striatal neurons and we unveil the precise molecular mechanism underlying this process: a phospholipase C/Ca 2ϩ /proline-rich tyrosine kinase 2/cJun N-terminal kinase pathway. Moreover, engagement of this intracellular signaling route was functionally active in the mouse dorsal striatum in vivo, as proven by the disruption of neuronal integrity and behavioral tasks. To analyze this effect anatomically, we manipulated G q-protein-dependent signaling selectively in neurons belonging to the direct or indirect striatal pathway. Acute G q-protein activation in direct-pathway or indirect-pathway neurons produced an enhancement or a decrease, respectively , of activity-dependent parameters. In contrast, sustained G q-protein activation impaired the functionality of direct-pathway and indirect-pathway neurons and disrupted the behavioral performance and electroencephalography-related activity tasks controlled by either anatomical framework. Collectively, these findings define the molecular mechanism and functional relevance of G q-protein-driven signals in striatal circuits under normal and overactivated states

Functional Organization of Locomotor Interneurons in the Ventral Lumbar Spinal Cord of the Newborn Rat

Although the mammalian locomotor CPG has been localized to the lumbar spinal cord, the functional-anatomical organization of flexor and extensor interneurons has not been characterized. Here, we tested the hypothesis that flexor and extensor interneuronal networks for walking are physically segregated in the lumbar spinal cord. For this purpose, we performed optical recordings and lesion experiments from a horizontally sectioned lumbar spinal cord isolated from neonate rats. This ventral hemi spinal cord preparation produces well-organized fictive locomotion when superfused with 5-HT/NMDA. The dorsal surface of the preparation was visualized using the Ca2+ indicator fluo-4 AM, while simultaneously monitoring motor output at ventral roots L2 and L5. Using calcium imaging, we provided a general mapping view of the interneurons that maintained a stable phase relationship with motor output. We showed that the dorsal surface of L1 segment contains a higher density of locomotor rhythmic cells than the other segments. Moreover, L1 segment lesioning induced the most important changes in the locomotor activity in comparison with lesions at the T13 or L2 segments. However, no lesions led to selective disruption of either flexor or extensor output. In addition, this study found no evidence of functional parcellation of locomotor interneurons into flexor and extensor pools at the dorsal-ventral midline of the lumbar spinal cord of the rat

Rôle du tronc chez les mammifères au cours de la locomotion (approche électrophysiologique et cinématique)

La locomotion résulte de phénomènes posturaux complexes qui nécessitent le fonctionnement intégré des membres antérieurs, postérieurs et du tronc. Le maintiens d un équilibre dynamique durant la propulsion vers l avant ne peut être réalisé que parce qu il existe des processus internes de coordination entrez les réseaux nerveux qui commandent la contraction rythmique de ces différents niveaux. Alors que la grande majorité des études sur la locomotion porte sur le fonctionnement des membres postérieurs, notre intérêt s est focalisé sur le rôle du tronc et l organisation des réseaux neuronaux spinaux sous-tendant son activité en coordination avec les membres. Trois approches différentes ont été réalisées : (1) cinématique permettant de visualiser dans l espace les mouvements du rat de sa naissance à l âge du sevrage ; (2) électrophysiologique sur préparation de moelle épinière isolée in vitro centrée sur les réseaux spinaux responsables de l activité motrice chez le rat nouveau-né ; (3) électromyographique pour déterminer le patron d activation des muscles axiaux chez l homme. Nos résultats montrent qu au cours du déplacement, le tronc se courbe rythmiquement chez le rat et l homme. Chez le rat, le développement modifie la sortie motrice en amplitude et en vitesse d exécution principalement. La courbe du tronc serait due à la propagation séquentielle de l onde motrice le long de la moelle épinière. Nos données suggèrent également que les réseaux responsables de la propagation métachronale des patrons moteurs au cours de la locomotion correspondent à ceux observés chez les invertébrés ou vertébrés inférieurs et seraient donc conservés à travers l évolution.Locomotion involves complex synergistic postural regulation requiring the integrated functioning of all the body musculature, including hind- and forelimb, trunk and neck muscles. Dynamic equilibrium during forward locomotion is preserved by internal process of coordination between neuronal that drive rhythmic contraction of this muscles. Although numerous studies have focused on understanding how the CNS controls hindlimb movements, very few studies has been devotes to understanding the functioning of neural networks that activate trunk muscles in coordination with limb movements. To answer approach these question three main approaches have been used. (1) a kinematic approach allowing to visualize from birth to weaning day, the rat movements in a 3-D environment ; (2) an electrophysiological approach on an in vitro isolated spinal cord preparation based on spinal neuronal networks responsible for motor activity in the newborn rat ; (3) an electromyographic approach to determine the pattern of activity of axial movements in human. Our results show that there is a rhythmic sequential change in trunk curvature during the step cycle. In rats, development modifies the amplitude an velocity of the motor output. The trunk bending could be related to the sequential propagation of the motor wave along the spinal cord. Our data suggest that the networks responsible for metachronal propagation of motor patterns during locomotion may correspond to those observed in vertebrates or lower vertebrates, and thus are highly conserved.BORDEAUX2-BU Sci.Homme/Odontol. (330632102) / SudocSudocFranceF