John Simmers
University of Bordeaux
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Featured researches published by John Simmers.
The Journal of Neuroscience | 2005
Laurent Juvin; John Simmers; Didier Morin
Soon after birth, freely moving quadrupeds can express locomotor activity with coordinated forelimb and hindlimb movements. To investigate the neural mechanisms underlying this coordination, we used an isolated spinal cord preparation from neonatal rats. Under bath-applied 5-HT, N-methyl-d,l-aspartate (NMA), and dopamine (DA), the isolated cord generates fictive locomotion in which homolateral cervicolumbar extensor motor bursts occur in phase opposition, as does bursting in homologous (left-right) extensor motoneurons. This coordination corresponded to a walking gait monitored with EMG recordings in the freely behaving animal. Functional decoupling of the cervical and lumbar generators in vitro by sucrose blockade at the thoracic cord level revealed independent rhythmogenic capabilities with similar cycle frequencies in the two locomotor regions. When the cord was partitioned at different thoracic levels and 5-HT/NMA/DA was applied to the more caudal compartment, the ability of the lumbar generators to drive their cervical counterparts increased with the proportion of chemically exposed thoracic segments. Blockade of synaptic inhibition at the lumbar level caused synchronous bilateral lumbar rhythmicity that, surprisingly, also was able to impose bilaterally synchronous bursting at the unblocked cervical level. Furthermore, after a midsagittal section from spinal segments C1 to T7, and during additional blockade of cervical synaptic inhibition, the cord exposed to 5-HT/NMA/DA continued to produce a coordinated fictive walking pattern similar to that observed in control. Thus, in the newborn rat, a caudorostral propriospinal excitability gradient appears to mediate interlimb coordination, which relies more on asymmetric axial connectivity (both excitatory and inhibitory) between the lumbar and cervical generators than on differences in their inherent rhythmogenic capacities.
The Journal of Physiology | 2004
Denis Combes; S. D. Merrywest; John Simmers; Keith T. Sillar
Amphibian metamorphosis includes a complete reorganization of an organisms locomotory system from axial‐based swimming in larvae to limbed propulsion in the young adult. At critical stages during this behavioural switch, larval and adult motor systems operate in the same animal, commensurate with a gradual and dynamic reconfiguration of spinal locomotor circuitry. To study this plasticity, we have developed isolated preparations of the spinal cord and brainstem from pre‐ to post‐metamorphic stages of the amphibian Xenopus laevis, in which spinal motor output patterns expressed spontaneously or in the presence of NMDA correlate with locomotor behaviour in the freely swimming animal. Extracellular ventral root recordings along the spinal cord of pre‐metamorphic tadpoles revealed motor output corresponding to larval axial swimming, whereas postmetamorphic animals expressed motor patterns appropriate for bilaterally synchronous hindlimb flexion–extension kicks. However, in vitro recordings from metamorphic climax stages, with the tail and the limbs both functional, revealed two distinct motor patterns that could occur either independently or simultaneously, albeit at very different frequencies. Activity at 0.5–1 Hz in lumbar ventral roots corresponded to bipedal extension–flexion cycles, while the second, faster pattern (2–5 Hz) recorded from tail ventral roots corresponded to larval‐like swimming. These data indicate that at intermediate stages during metamorphosis separate networks, one responsible for segmentally organized axial locomotion and another for more localized appendicular rhythm generation, coexist in the spinal cord and remain functional after isolation in vitro. These preparations now afford the opportunity to explore the cellular basis of locomotor network plasticity and reconfiguration necessary for behavioural changes during development.
The Journal of Physiology | 2007
Laurent Juvin; John Simmers; Didier Morin
The temporal properties of limb motoneuron bursting underlying quadrupedal locomotion were investigated in isolated spinal cord preparations (without or with brainstem attached) taken from 0 to 4‐day‐old rats. When activated either with differing combinations of N‐methyl‐d,l‐aspartate, serotonin and dopamine, or by electrical stimulation of the brainstem, the spinal cord generated episodes of fictive locomotion with a constant phase relationship between cervical and lumbar ventral root bursts. Alternation occurred between ipsi‐ and contra‐lateral flexor and extensor motor root bursts, and the cervical and lumbar locomotor networks were always active in a diagonal coordination pattern that corresponded to fictive walking. However, unlike typical locomotion in adult animals in which extensor motoneuron bursts vary more with cycle period than flexor bursts, in the isolated neonatal cord, an increase in fictive locomotor speed was associated with a decrease in the durations of both extensor and flexor bursts, at cervical and lumbar levels. To determine whether this symmetry in flexor/extensor phase durations derived from the absence of sensory feedback that is normally provided from the limbs during intact animal locomotion, EMG recordings were made from hindlimb‐attached spinal cords during drug‐induced locomotor‐like movements. Under these conditions, the duration of extensor muscle bursts increased with cycle period, while flexor burst durations now tended to remain constant. Moreover, after a complete dorsal rhizotomy, this extensor dominant pattern was replaced by flexor and extensor muscle bursts of similar duration. In vivo and in vitro experiments were also conducted on older postnatal (P10–12) rats at an age when body‐supported adult‐like locomotion occurs. Here again, characteristic extensor‐dominated burst patterns observed during intact treadmill locomotion were replaced by symmetrical patterns during fictive locomotion expressed by the chemically activated isolated spinal cord, further indicating that sensory inputs are normally responsible for imposing extensor biasing on otherwise symmetrically alternating extensor/flexor oscillators.
The Journal of Neuroscience | 2012
Laurent Juvin; Jean-Patrick Le Gal; John Simmers; Didier Morin
Effective quadrupedal locomotion requires a close coordination between the spatially distant central pattern generators (CPGs) controlling forelimb and hindlimb movements. Using isolated preparations of the neonatal rat spinal cord, we explore the role of intervening thoracic circuitry in cervicolumbar CPG coordination and the contribution to this remote coupling of limb somatosensory inputs. In preparations activated with bath-applied N-methyl-d,l-aspartate, serotonin, and dopamine, the coordination between locomotor-related bursts recorded in cervical and lumbar ventral roots was substantially weakened, although not abolished, when the thoracic segments were selectively withheld from neurochemical stimulation or were exposed to a low Ca2+ solution to block synaptic transmission. Moreover, cervicolumbar CPG coordination was reduced after a thoracic midsagittal section, suggesting that cross-cord projections participate in the anteroposterior coupling. In quiescent preparations, either cyclic or tonic electrical stimulation of low-threshold afferent pathways in C8 or L2 dorsal roots (DRs) could elicit coordinated ventral root bursting at both cervical and lumbar levels via an activation of the underlying CPG networks. When lumbar rhythmogenesis was prevented by local synaptic transmission blockade, L2 DR stimulation could still drive left–right alternating cervical bursting in preparations otherwise exposed to normal bathing medium. In contrast, when the cervical generators were selectively blocked, C8 DR stimulation was unable to activate the lumbar CPGs. Thus, in the newborn rat, anteroposterior limb coordination relies on active burst generation within midcord thoracic circuitry that additionally conveys ascending and weaker descending coupling influences of distant limb proprioceptive inputs to the cervical and lumbar generators, respectively.
Journal of Neurophysiology | 2012
Stefan Clemens; Aude Belin-Rauscent; John Simmers; Denis Combes
The role of dopamine in regulating spinal cord function is receiving increasing attention, but its actions on spinal motor networks responsible for rhythmic behaviors remain poorly understood. Here, we have explored the modulatory influence of dopamine on locomotory central pattern generator (CPG) circuitry in the spinal cord of premetamorphic Xenopus laevis tadpoles. Bath application of exogenous dopamine to isolated brain stem-spinal cords exerted divergent dose-dependent effects on spontaneous episodic patterns of locomotory-related activity recorded extracellularly from spinal ventral roots. At low concentration (2 μM), dopamine reduced the occurrence of bursts and fictive swim episodes and increased episode cycle periods. In contrast, at high concentration (50 μM) dopamine reversed its actions on fictive swimming, now increasing both burst and swim episode occurrences while reducing episode periods. The low-dopamine effects were mimicked by the D2-like receptor agonists bromocriptine and quinpirole, whereas the D1-like receptor agonist SKF 38393 reproduced the effects of high dopamine. Furthermore, the motor response to the D1-like antagonist SCH 23390 resembled that to the D2 agonists, whereas the D2-like antagonist raclopride mimicked the effects of the D1 agonist. Together, these findings indicate that dopamine plays an important role in modulating spinal locomotor activity. Moreover, the transmitters opposing influences on the same target CPG are likely to be accomplished by a specific, concentration-dependent recruitment of independent D2- and D1-like receptor signaling pathways that differentially mediate inhibitory and excitatory actions.
Current Biology | 2008
Denis Combes; Didier Le Ray; François Lambert; John Simmers; Hans Straka
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.
European Journal of Neuroscience | 2000
Pierre Meyrand; Serge Faumont; John Simmers; Andrew E. Christie; Michael P. Nusbaum
Phylogenetic comparison can reveal general principles governing the organization and neuromodulation of neural networks. Suitable models for such an approach are the pyloric and gastric motor networks of the crustacean stomatogastric ganglion (STG). These networks, which have been well studied in several species, are extensively modulated by projection neurons originating in higher‐order ganglia. Several of these have been identified in different decapod species, including the paired modulatory proctolin neuron (MPN) in the crab Cancer borealis [Nusbaum & Marder (1989) J. Neurosci., 9,1501–1599; Nusbaum & Marder (1989) , J. Neurosci., 9, 1600–1607] and the apparently equivalent neuron pair, called GABA (γ‐aminobutyric acid) neurons 1 and 2 (GN1/2), in the lobster Homarus gammarus [ Cournil et al. (1990) J. Neurocytol., 19, 478–493]. The morphologies of MPN and GN1/2 are similar, and both exhibit GABA‐immunolabelling. However, unlike MPN, GN1/2 does not contain the peptide transmitter proctolin. Instead, GN1/2, but not MPN, is immunoreactive for the neuropeptides related to cholecystokinin (CCK) and FLRFamide. Nonetheless, GN1/2 excitation of the lobster pyloric rhythm is similar to the proctolin‐mediated excitation of the crab pyloric rhythm by MPN. In contrast, GN1/2 and MPN both use GABA but produce opposite effects on the gastric mill rhythm. While MPN stimulation produces a GABA‐mediated suppression of the gastric rhythm [ Blitz & Nusbaum (1999) J. Neurosci., 19, 6774–6783], GN1/2 activates or enhances gastric rhythmicity. These results highlight the care needed when generalizing neuronal organization and function across related species. Here we show that the ‘same’ neuron in different species does not contain the same neurotransmitter complement, nor does it exert all of the same effects on its postsynaptic targets. Conversely, a different transmitter phenotype is not necessarily associated with a qualitative change in the way that a modulatory neuron influences target network activity.
Current Opinion in Neurobiology | 1998
Valérie S Fénelon; Béatrice Casasnovas; John Simmers; Pierre Meyrand
In contrast to the wealth of knowledge about the organizational rules of adult central pattern generators, far less is known about how these networks are assembled during development. The basic architecture for adult central pattern generators appears early in development but different generators may follow completely different developmental pathways to reach maturity. Recent evidence suggests that neuromodulatory inputs, in addition to their short-term adaptive control of central pattern generator activity, play a crucial role in both the final developmental tuning and the long-term maintenance of adult network function.
The Journal of Neuroscience | 2007
Romuald Nargeot; Christine Petrissans; John Simmers
Motivated behaviors comprise appetitive actions whose occurrence results partly from an internally driven incentive to act. Such impulsive behavior can also be regulated by external rewarding stimuli that, through learning processes, can lead to accelerated and seemingly automatic, compulsive-like recurrences of the rewarded act. Here, we explored such behavioral plasticity in Aplysia by analyzing how appetitive reward stimulation in a form of operant conditioning can modify a goal-directed component of the animals food-seeking behavior. In naive animals, protraction/retraction cycles of the tongue-like radula are expressed sporadically with highly variable interbite intervals. In contrast, animals that were previously given a food-reward stimulus in association with each spontaneous radula bite now expressed movement cycles with an elevated frequency and a stereotyped rhythmic organization. This rate increase and regularization, which was retained for several hours after training, depended on both the reward quality and its contingency because accelerated, stereotyped biting was not induced in animals that had previously received a less-palatable food stimulus or had been subjected to nonassociative reward stimulation. Neuronal correlates of these learning-induced changes were also expressed in the radula motor pattern-generating circuitry of isolated buccal ganglia. In such in vitro preparations, moreover, manipulation of the burst frequency of the bilateral motor pattern-initiating B63 interneurons indicated that the regularization of radula motor pattern generation in contingently trained animals occurred separately from an increase in cycle rate, thereby suggesting independent processes of network plasticity. These data therefore suggest that operant conditioning can induce compulsive-like actions in Aplysia feeding behavior and provide a substrate for a cellular analysis of the underlying mechanisms.
Developmental Neurobiology | 2012
Hans Straka; John Simmers
The amphibian Xenopus laevis represents a highly amenable model system for exploring the ontogeny of central neural networks, the functional establishment of sensory‐motor transformations, and the generation of effective motor commands for complex behaviors. Specifically, the ability to employ a range of semi‐intact and isolated preparations for in vitro morphophysiological experimentation has provided new insights into the developmental and integrative processes associated with the generation of locomotory behavior during changing life styles. In vitro electrophysiological studies have begun to explore the functional assembly, disassembly and dynamic plasticity of spinal pattern generating circuits as Xenopus undergoes the developmental switch from larval tail‐based swimming to adult limb‐based locomotion. Major advances have also been made in understanding the developmental onset of multisensory signal processing for reactive gaze and posture stabilizing reflexes during self‐motion. Additionally, recent evidence from semi‐intact animal and isolated CNS experiments has provided compelling evidence that in Xenopus tadpoles, predictive feed‐forward signaling from the spinal locomotor pattern generator are engaged in minimizing visual disturbances during tail‐based swimming. This new concept questions the traditional view of retinal image stabilization that in vertebrates has been exclusively attributed to sensory‐motor transformations of body/head motion‐detecting signals. Moreover, changes in visuomotor demands associated with the developmental transition in propulsive strategy from tail‐ to limb‐based locomotion during metamorphosis presumably necessitates corresponding adaptive alterations in the intrinsic spinoextraocular coupling mechanism. Consequently, Xenopus provides a unique opportunity to address basic questions on the developmental dynamics of neural network assembly and sensory‐motor computations for vertebrate motor behavior in general.