Didier Le Ray

Central control components of a 'simple' stretch reflex.

The monosynaptic stretch reflex is a fundamental feature of sensory-motor organization in most animal groups. In isolation, it serves largely as a negative feedback devoted to postural controls; however, when it is involved in diverse movements, it can be modified by central command circuits. In order to understand the implications of such modifications, a model system has been chosen that has been studied at many different levels: the crayfish walking system. Recent studies have revealed several levels of control and modulation (for example, at the levels of the sensory afferent and the output synapse from the sensory afferent, and via changes in the membrane properties of the postsynaptic neuron) that operate complex and highly adaptive sensory-motor processing. During a given motor task, such mechanisms reshape the sensory message completely, such that the stretch reflex becomes a part of the central motor command.

An intrinsic feed-forward mechanism for vertebrate gaze stabilization

Summary Accurate perception of the visual world plays a major role in animal survival. All vertebrates, whether running, swimming or flying, are confronted with the effects of their locomotor actions on the ability to perceive their surrounding environment [1]. The potential consequences of self-generated body motion include head movements that cause retinal image displacement with a resultant degradation of visual information processing. In order to maintain visual acuity during locomotion, retinal image drift must be counteracted by dynamic compensatory eye and/or head-adjustments that derive from sensory-motor transformations of vestibulo-ocular, optokinetic and proprioceptive inputs [2]. Here we report that efference copies of rhythmic neural signals produced by locomotor pattern-generating circuitry within the spinal cord of larval Xenopus laevis are conveyed to the brainstem extraocular motor nuclei and potentially contribute to gaze stabilization during locomotion. Appropriate spinal network-extraocular motor coupling not only persisted during actual undulatory tail movements in semi-intact preparations, but also during fictive locomotion in isolated brainstem-spinal cords without any movement-derived sensory inputs. This suggests that inherent feed-forward signalling may be used in combination with sensory feed-back to counteract the visual consequences of tadpole self-motion, with major implications for understanding gaze control in general.

Direct glutamate-mediated presynaptic inhibition of sensory afferents by the postsynaptic motor neurons

An inu2003vitro preparation of the crayfish central nervous system was used to study a negative feedback control exerted by the glutamatergic motor neurons (MNs) on to their presynaptic cholinergic sensory afferents. This negative control consists in small amplitude, slowly developing depolarizations of the primary afferents (sdPADs) strictly timed with MN bursts. They were not blocked by picrotoxin, but were sensitive to glutamate non‐N‐methyl‐d‐aspartate (NMDA) antagonists. Intracellular recordings were performed within thin branches of sensory terminals while electrical antidromic stimulation were applied to the motor nerves, or while glutamate (the MN neurotransmitter) was pressure‐applied close to the recording site. Electrical motor nerve stimulations and glutamate pressure application had similar effects on to sensory terminals issued from the coxo‐basipodite chordotonal organ (CBTs): like sdPADs, both stimulation‐induced depolarizations were picrotoxin‐resistant and were dramatically reduced by non‐NMDA antagonist bath application. These results indicate that sdPADs are likely directly produced by MNs during locomotor activity. A functional scheme is proposed.

Opposing Aminergic Modulation of Distinct Spinal Locomotor Circuits and Their Functional Coupling during Amphibian Metamorphosis

The biogenic amines serotonin (5-HT) and noradrenaline (NA) are well known modulators of central pattern-generating networks responsible for vertebrate locomotion. Here we have explored monoaminergic modulation of the spinal circuits that generate two distinct modes of locomotion in the metamorphosing frog Xenopus laevis. At metamorphic climax when propulsion is achieved by undulatory larval tail movements and/or by kicking of the newly developed adult hindlimbs, the underlying motor networks remain spontaneously active in vitro, producing either separate fast axial and slow appendicular rhythms or a single combined rhythm that drives coordinated tail-based and limb-based swimming in vivo. In isolated spinal cords already expressing distinct axial and limb rhythms, bath-applied 5-HT induced coupled network activity through an opposite slowing of axial rhythmicity (by increasing motoneuron burst and cycle durations) and an acceleration of limb rhythmicity (by decreasing burst and cycle durations). In contrast, in preparations spontaneously expressing coordinated fictive locomotion, exogenous NA caused a dissociation of spinal activity into separate faster axial and slower appendicular rhythms by decreasing and increasing burst and cycle durations, respectively. Moreover, in preparations from premetamorphic and postmetamorphic animals that express exclusively axial-based or limb-based locomotion, 5-HT and NA modified the developmentally independent rhythms in a similar manner to the amines opposing effects on the coexisting circuits at metamorphic climax. Thus, by exerting differential modulatory actions on one network that are opposite to their influences on a second adjacent circuit, these two amines are able to precisely regulate the functional relationship between different rhythmogenic networks in a developing vertebrates spinal cord.

Development and neuromodulation of spinal locomotor networks in the metamorphosing frog

Metamorphosis in the anuran frog, Xenopus laevis, involves profound structural and functional transformations in most of the organisms physiological systems as it encounters a complete alteration in body plan, habitat, mode of respiration and diet. The metamorphic process also involves a transition in locomotory strategy from axial-based undulatory swimming using alternating contractions of left and right trunk muscles, to bilaterally-synchronous kicking of the newly developed hindlimbs in the young adult. At critical stages during this behavioural switch, functional larval and adult locomotor systems co-exist in the same animal, implying a progressive and dynamic reconfiguration of underlying spinal circuitry and neuronal properties as limbs are added and the tail regresses. To elucidate the neurobiological basis of this developmental process, we use electrophysiological, pharmacological and neuroanatomical approaches to study isolated in vitro brain stem/spinal cord preparations at different metamorphic stages. Our data show that the emergence of secondary limb motor circuitry, as it supersedes the primary larval network, spans a developmental period when limb circuitry is present but not functional, functional but co-opted into the axial network, functionally separable from the axial network, and ultimately alone after axial circuitry disappears with tail resorption. Furthermore, recent experiments on spontaneously active in vitro preparations from intermediate metamorphic stage animals have revealed that the biogenic amines serotonin (5-HT) and noradrenaline (NA) exert short-term adaptive control over circuit activity and inter-network coordination: whereas bath-applied 5-HT couples axial and appendicular rhythms into a single unified pattern, NA has an opposite decoupling effect. Moreover, the progressive and region-specific appearance of spinal cord neurons that contain another neuromodulator, nitric oxide (NO), suggests it plays a role in the maturation of limb locomotor circuitry. In summary, during Xenopus metamorphosis the network responsible for limb movements is progressively segregated from an axial precursor, and supra- and intra-spinal modulatory inputs are likely to play crucial roles in both its functional flexibility and maturation.

Metamorphosis-Induced Changes in the Coupling of Spinal Thoraco-Lumbar Motor Outputs During Swimming in Xenopus laevis

Anuran metamorphosis includes a complete remodeling of the animals biomechanical apparatus, requiring a corresponding functional reorganization of underlying central neural circuitry. This involves changes that must occur in the coordination between the motor outputs of different spinal segments to harmonize locomotor and postural functions as the limbs grow and the tail regresses. In premetamorphic Xenopus laevis tadpoles, axial motor output drives rostrocaudally propagating segmental myotomal contractions that generate propulsive body undulations. During metamorphosis, the anterior axial musculature of the tadpole progressively evolves into dorsal muscles in the postmetamorphic froglet in which some of these back muscles lose their implicit locomotor function to serve exclusively in postural control in the adult. To understand how locomotor and postural systems interact during locomotion in juvenile Xenopus, we have investigated the coordination between postural back and hindlimb muscle activity during free forward swimming. Axial/dorsal muscles, which contract in bilateral alternation during undulatory swimming in premetamorphic tadpoles, change their left-right coordination to become activated in phase with bilaterally synchronous hindlimb extensions in locomoting juveniles. Based on in vitro electrophysiological experiments as well as specific spinal lesions in vivo, a spinal cord region was delimited in which propriospinal interactions are directly responsible for the coordination between leg and back muscle contractions. Our findings therefore indicate that dynamic postural adjustments during adult Xenopus locomotion are mediated by local intraspinal pathways through which the lumbar generator for hindlimb propulsive kicking provides caudorostral commands to thoracic spinal circuitry controlling the dorsal trunk musculature.

Spinal Efference Copy Signaling and Gaze Stabilization during Locomotion in Juvenile Xenopus Frogs

In swimming Xenopus laevis tadpoles, gaze stabilization is achieved by efference copies of spinal locomotory CPG output that produce rhythmic extraocular motor activity appropriate for minimizing motion-derived visual disturbances. During metamorphosis, Xenopus switches its locomotory mechanism from larval tail-based undulatory movements to bilaterally synchronous hindlimb kick propulsion in the adult. The change in locomotory mode leads to body motion dynamics that no longer require conjugate left–right eye rotations for effective retinal image stabilization. Using in vivo kinematic analyses, in vitro electrophysiological recordings and specific CNS lesions, we have investigated spino-extraocular motor coupling in the juvenile frog and the underlying neural pathways to understand how gaze control processes are altered in accordance with the animals change in body plan and locomotor strategy. Recordings of extraocular and limb motor nerves during spontaneous “fictive” swimming in isolated CNS preparations revealed that there is indeed a corresponding change in spinal efference copy control of extraocular motor output. In contrast to fictive larval swimming where alternating bursts occur in bilateral antagonistic horizontal extraocular nerves, during adult fictive limb-kicking, these motor nerves are synchronously active in accordance with the production of convergent eye movements during the linear head accelerations resulting from forward propulsion. Correspondingly, the neural pathways mediating spino-extraocular coupling have switched from contralateral to strictly ipsilateral ascending influences that ensure a coactivation of bilateral extraocular motoneurons with synchronous left–right limb extensions. Thus, adaptive developmental plasticity during metamorphosis enables spinal CPG-driven extraocular motor activity to match the changing requirements for eye movement control during self-motion.