From tadpole to adult frog locomotion.

The transition from larval to adult locomotion in the anuran, Xenopus laevis, involves a dramatic switch from axial to appendicular swimming including intermediate stages when the tail and hindlimbs co-exist and contribute to propulsion. Hatchling tadpole swimming is generated by an axial central pattern generator (CPG) which matures rapidly during early larval life. During metamorphosis, the developing limbs are controlled by a de novo appendicular CPG driven initially by the axial system before segregating to allow both systems to operate together or independently.

Locomotion-induced ocular motor behavior in larval Xenopus is developmentally tuned by visuo-vestibular reflexes.

Locomotion in vertebrates is accompanied by retinal image-stabilizing eye movements that derive from sensory-motor transformations and predictive locomotor efference copies. During development, concurrent maturation of locomotor and ocular motor proficiency depends on the structural and neuronal capacity of the motion detection systems, the propulsive elements and the computational capability for signal integration. In developing Xenopus larvae, we demonstrate an interactive plasticity of predictive locomotor efference copies and multi-sensory motion signals to constantly elicit dynamically adequate eye movements during swimming.

Metamorphosing motor networks.

Many animals undergo a transition during their lifetime from a larval to an adult form, a major developmental change known as metamorphosis. This developmental process, which involves behavioural, morphological, physiological and biochemical changes, has a broad phylogenetic distribution, occurring in diverse branches of the animal kingdom, from invertebrates (molluscs, arthropods, tunicates) to certain classes of vertebrates, including amphibians (Figure 1). This phenomenon, which has fascinated biologists for centuries, remains an attractive experimental model for studying mechanisms of post-embryonic development as well as molecular mechanisms underlying hormonal regulation.

Temporal Relationship of Ocular and Tail Segmental Movements Underlying Locomotor-Induced Gaze Stabilization During Undulatory Swimming in Larval Xenopus.

In larval xenopus, locomotor-induced oculomotor behavior produces gaze-stabilizing eye movements to counteract the disruptive effects of tail undulation during swimming. While neuronal circuitries responsible for feed-forward intrinsic spino-extraocular signaling have recently been described, the resulting oculomotor behavior remains poorly understood. Conveying locomotor CPG efference copy, the spino-extraocular motor command coordinates the multi-segmental rostrocaudal spinal rhythmic activity with the extraocular motor activity.

Adaptive plasticity of spino-extraocular motor coupling during locomotion in metamorphosing Xenopus laevis.

During swimming in the amphibian ITALIC! Xenopus laevis, efference copies of rhythmic locomotor commands produced by the spinal central pattern generator (CPG) can drive extraocular motor output appropriate for producing image-stabilizing eye movements to offset the disruptive effects of self-motion. During metamorphosis, ITALIC! X. laevisremodels its locomotor strategy from larval tail-based undulatory movements to bilaterally synchronous hindlimb kicking in the adult.

A behaviorally related developmental switch in nitrergic modulation of locomotor rhythmogenesis in larval Xenopus tadpoles.

Locomotor control requires functional flexibility to support an animal's full behavioral repertoire. This flexibility is partly endowed by neuromodulators, allowing neural networks to generate a range of motor output configurations. In hatchling Xenopus tadpoles, before the onset of free-swimming behavior, the gaseous modulator nitric oxide (NO) inhibits locomotor output, shortening swim episodes and decreasing swim cycle frequency.

Generation of BAC transgenic tadpoles enabling live imaging of motoneurons by using the urotensin II-related peptide (ust2b) gene as a driver.

Xenopus is an excellent tetrapod model for studying normal and pathological motoneuron ontogeny due to its developmental morpho-physiological advantages. In mammals, the urotensin II-related peptide (UTS2B) gene is primarily expressed in motoneurons of the brainstem and the spinal cord. Here, we show that this expression pattern was conserved in Xenopus and established during the early embryonic development, starting at the early tailbud stage.

Neuromodulation in developing motor microcircuits.

Neuromodulation confers operational flexibility on motor network output and resulting behaviour. Furthermore, neuromodulators play crucial long-term roles in the assembly and maturational shaping of the same networks as they develop. Although previous studies have identified such modulator-dependent contributions to microcircuit ontogeny, some of the underlying mechanisms are only now being elucidated.

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.

Gaze stabilization by efference copy signaling without sensory feedback during vertebrate locomotion.

Background: Self-generated body movements require compensatory eye and head adjustments in order to avoid perturbation of visual information processing. Retinal image stabilization is traditionally ascribed to the transformation of visuovestibular signals into appropriate extraocular motor commands for compensatory ocular movements. During locomotion, however, intrinsic "efference copies" of the motor commands deriving from spinal central pattern generator (CPG) activity potentially offer a reliable and rapid mechanism for image stabilization, in addition to the slower contribution of movement-encoding sensory inputs.

A switch in aminergic modulation of locomotor CPG output during amphibian metamorphosis.

In the South African clawed frog, Xenopus laevis, a complete functional switch in the mode of locomotion occurs during development from axial, undulatory, tail-based swimming in post-hatching tadpoles to limb-based kick propulsion in the adult froglet. At key stages during the metamorphosis from tadpole to frog both locomotor systems are present, co-functional and subject to modulation by the two ubiquitous biogenic amines, serotonin (5-HT) and noradrenaline (NA), arising from the brainstem. Here we review evidence on the roles of 5-HT and NA in the early maturation and dynamic modulation of spinal locomotor circuitry in the postembryonic tadpole and describe the way in which the modulatory effects of the two amines, which are always in opposition, subsequently switch during the metamorphic period of development.

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.

Multiple mechanisms for integrating proprioceptive inputs that converge on the same motor pattern-generating network.

Movement-derived sensory feedback adapts centrally generated motor programs to changing behavioral demands. Motor circuit output may also be shaped by distinct proprioceptive systems with different central actions, although little is known about the integrative processes by which such convergent sensorimotor regulation occurs. Here, we explore the combined actions of two previously identified proprioceptors on the gastric mill motor network in the lobster stomatogastric nervous system.

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 animal's 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.

Neuromodulation and developmental plasticity in the locomotor system of anuran amphibians during metamorphosis.

Metamorphosis in frogs has long fascinated laymen and scientists alike. This remarkable developmental transformation involves the simultaneous remodelling of almost every organ in the body, including the gut, associated with a switch in diet from filter feeder to predator, and the visual system, from laterally-directed monocular to forward-directed binocular vision. In the context of locomotion there is the complete loss of the tail, the main structure involved in generating thrust during swimming in larvae, and the gain of the limbs which produce rhythmic extension-flexion kicks during swimming and jumping.

Developmental and regional expression of NADPH-diaphorase/nitric oxide synthase in spinal cord neurons correlates with the emergence of limb motor networks in metamorphosing Xenopus laevis.

Metamorphosis in anuran amphibians requires a complete transformation in locomotor strategy from undulatory tadpole swimming to adult quadrupedal propulsion. The underlying reconfiguration of spinal networks may be influenced by various neuromodulators including nitric oxide, which is known to play an important role in CNS development and plasticity in diverse species, including metamorphosis of amphibians. Using NADPH-diaphorase (NADPH-d) staining and neuronal nitric oxide synthase (nNOS) immunofluorescence labelling, the expression and developmental distribution of NOS-containing neurons in the spinal cord and brainstem were analysed in all metamorphic stages of Xenopus laevis.

Reconfiguration of multiple motor networks by short- and long-term actions of an identified modulatory neuron.

The pyloric and gastric motor pattern-generating networks in the stomatogastric ganglion of the lobster Homarus gammarus are reconfigured into a new functional circuit by burst discharge in an identified pair of modulatory projection interneurons, originally named the pyloric suppressor (PS) neurons because of their inhibitory effects on pyloric network activity. Here we elucidate the actions of the PS neurons on individual members of the neighbouring gastric circuit, as well as describing their ability to alter synaptic coupling between the two networks. PS neuron firing has two distinct effects on gastric network activity: an initial short-lasting action mediated by transient inhibition of most gastric motoneurons, followed by a long-lasting circuit activation associated with a prolonged PS-evoked depolarization of the medial gastric (MG) motoneuron and the single network interneuron, Int1.

In vivo analysis of proprioceptive coding and its antidromic modulation in the freely behaving crayfish.

Although sensory nerves in vitro are known to convey both orthodromic (sensory) and antidromic (putatively modulating) action potentials, in most cases very little is known about their bidirectional characteristics in intact animals. Here, we have investigated both the sensory coding properties and antidromic discharges that occur during real walking in the freely behaving crayfish. The activity of the sensory nerve innervating the proprioceptor CBCO, a chordotonal organ that monitors both angular movement and position of the coxo-basipodite (CB) joint, which is implicated in vertical leg movements, was recorded chronically along with the electromyographic activity of the muscles that control CB joint movements.

Rare and spatially segregated release sites mediate a synaptic interaction between two identified network neurons.

Laser-scanning confocal microscopy (LSCM), electron microcopy (EM), and cellular electrophysiology were used in combination to study the structural basis of an inhibitory synapse between two identified neurons of the same network. To achieve this, we examined the chemical inhibitory synapse between identified neurons belonging to the lobster (Homarus gammarus) pyloric network: the pyloric dilator (PD) and the lateral pyloric (LP) neurons. In order to visualize simultaneously these two neurons, we used intrasomatic injection of Lucifer Yellow (LY) in one and rhodamine/horseradish peroxydase (HRP) in the other.