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There is a lack of experimental methods in genetically tractable mouse models to analyze the developmental period at which newborns mature weight-bearing locomotion. To overcome this deficit, we introduce methods to study L-DOPA induced air-stepping in mice at postnatal day 7 (P7) and P10. Air-stepping is a stereotypic rhythmic behavior that resembles mouse walking overground locomotion, but without constraints imposed by weight-bearing, postural adjustments or sensory feedback. We propose that air-stepping represents the functional organization of early spinal circuits coordinating limb movements. After subcutaneous injection of L-DOPA (0.5 mg/g), we recorded air-stepping movements in all four limbs and electromyographic (EMG) activity from ankle flexor (tibialis anterior, TA) and extensor (lateral gastrocnemius, LG) muscles. Using DeepLabCut pose estimation we analyzed rhythmicity and limb coordination. We demonstrate steady rhythmic stepping of similar duration from P7 to P10, but with some fine-tuning of interlimb coordination with age. Hindlimb joints undergo a greater range of flexion at older ages indicating maturation of flexion-extension cycles as the animal starts to walk. Electromyographic recording of TA and LG show alternation, but with more focused activation particularly in the LG from P7 to P10. We discuss similarities with neonatal rat L-DOPA induced air-stepping and infant assisted walking. We conclude that limb coordination and muscle activations recorded with this method represent basic spinal cord circuitry for limb control in neonates and paves the way for future investigations on the development of rhythmic limb control in genetic or disease models with correctly or erroneously developing motor circuitry.
There is a lack of experimental methods in genetically tractable mouse models to analyze the developmental period at which newborns mature weight-bearing locomotion. To overcome this deficit, we introduce methods to study L-DOPA induced air-stepping in mice at postnatal day 7 (P7) and P10. Air-stepping is a stereotypic rhythmic behavior that resembles mouse walking overground locomotion, but without constraints imposed by weight-bearing, postural adjustments or sensory feedback. We propose that air-stepping represents the functional organization of early spinal circuits coordinating limb movements. After subcutaneous injection of L-DOPA (0.5 mg/g), we recorded air-stepping movements in all four limbs and electromyographic (EMG) activity from ankle flexor (tibialis anterior, TA) and extensor (lateral gastrocnemius, LG) muscles. Using DeepLabCut pose estimation we analyzed rhythmicity and limb coordination. We demonstrate steady rhythmic stepping of similar duration from P7 to P10, but with some fine-tuning of interlimb coordination with age. Hindlimb joints undergo a greater range of flexion at older ages indicating maturation of flexion-extension cycles as the animal starts to walk. Electromyographic recording of TA and LG show alternation, but with more focused activation particularly in the LG from P7 to P10. We discuss similarities with neonatal rat L-DOPA induced air-stepping and infant assisted walking. We conclude that limb coordination and muscle activations recorded with this method represent basic spinal cord circuitry for limb control in neonates and paves the way for future investigations on the development of rhythmic limb control in genetic or disease models with correctly or erroneously developing motor circuitry.
L-DOPA, the precursor of catecholamines, exerts a pro-locomotor action in several vertebrate species, including newborn rats. Here, we tested the hypothesis that decreasing the degradation of monoamines can promote the pro-locomotor action of a low, subthreshold dose of L-DOPA in five-day-old rats. The activity of the degrading pathways involving monoamine oxidases or catechol-O-methyltransferase was impaired by injecting nialamide or tolcapone, respectively. At this early post-natal stage, the capacity of the drugs to trigger locomotion was investigated by monitoring the air-stepping activity expressed by the animals suspended in a harness above the ground. We show that nialamide (100 mg/kg) or tolcapone (100 mg/kg), without effect on their own promotes maximal expression of air-stepping sequences in the presence of a sub-effective dose of L-DOPA (25 mg/kg). Tissue measurements of monoamines (dopamine, noradrenaline, serotonin and some of their metabolites) in the cervical and lumbar spinal cord confirmed the regional efficacy of each inhibitor toward their respective enzyme. Our experiments support the idea that the raise of monoamines boost L-DOPA’s locomotor action. Considering that both inhibitors differently altered the spinal monoamines levels in response to L-DOPA, our data also suggest that maximal locomotor response can be reached with different monoamines environment.
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