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      Maturation of the Locomotor Circuitry in Children With Cerebral Palsy

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          Abstract

          The first years of life represent an important phase of maturation of the central nervous system, processing of sensory information, posture control and acquisition of the locomotor function. Cerebral palsy (CP) is the most common group of motor disorders in childhood attributed to disturbances in the fetal or infant brain, frequently resulting in impaired gait. Here we will consider various findings about functional maturation of the locomotor output in early infancy, and how much the dysfunction of gait in children with CP can be related to spinal neuronal networks vs. supraspinal dysfunction. A better knowledge about pattern generation circuitries in infancy may improve our understanding of developmental motor disorders, highlighting the necessity for regulating the functional properties of abnormally developed neuronal locomotor networks as a target for early sensorimotor rehabilitation. Various clinical approaches and advances in biotechnology are also considered that might promote acquisition of the locomotor function in infants at risk for locomotor delays.

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          Most cited references193

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          Early, Accurate Diagnosis and Early Intervention in Cerebral Palsy: Advances in Diagnosis and Treatment.

          Cerebral palsy describes the most common physical disability in childhood and occurs in 1 in 500 live births. Historically, the diagnosis has been made between age 12 and 24 months but now can be made before 6 months' corrected age.
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            Decoding the organization of spinal circuits that control locomotion.

            Ole Kiehn (2016)
            Unravelling the functional operation of neuronal networks and linking cellular activity to specific behavioural outcomes are among the biggest challenges in neuroscience. In this broad field of research, substantial progress has been made in studies of the spinal networks that control locomotion. Through united efforts using electrophysiological and molecular genetic network approaches and behavioural studies in phylogenetically diverse experimental models, the organization of locomotor networks has begun to be decoded. The emergent themes from this research are that the locomotor networks have a modular organization with distinct transmitter and molecular codes and that their organization is reconfigured with changes to the speed of locomotion or changes in gait.
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              Mechanisms underlying spontaneous patterned activity in developing neural circuits.

              Patterned, spontaneous activity occurs in many developing neural circuits, including the retina, the cochlea, the spinal cord, the cerebellum and the hippocampus, where it provides signals that are important for the development of neurons and their connections. Despite there being differences in adult architecture and output across these various circuits, the patterns of spontaneous network activity and the mechanisms that generate it are remarkably similar. The mechanisms can include a depolarizing action of GABA (gamma-aminobutyric acid), transient synaptic connections, extrasynaptic transmission, gap junction coupling and the presence of pacemaker-like neurons. Interestingly, spontaneous activity is robust; if one element of a circuit is disrupted another will generate similar activity. This research suggests that developing neural circuits exhibit transient and tunable features that maintain a source of correlated activity during crucial stages of development.
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                Author and article information

                Contributors
                Journal
                Front Bioeng Biotechnol
                Front Bioeng Biotechnol
                Front. Bioeng. Biotechnol.
                Frontiers in Bioengineering and Biotechnology
                Frontiers Media S.A.
                2296-4185
                18 August 2020
                2020
                : 8
                : 998
                Affiliations
                [1] 1Laboratory of Neuromotor Physiology, IRCCS Santa Lucia Foundation , Rome, Italy
                [2] 2Department of Pediatric Neurorehabilitation, IRCCS Santa Lucia Foundation , Rome, Italy
                [3] 3Centre of Space Bio-medicine and Department of Systems Medicine, University of Rome “Tor Vergata” , Rome, Italy
                [4] 4Laboratory of Neurobiology of Motor Control, Institute for Information Transmission Problems , Moscow, Russia
                Author notes

                Edited by: Leonardo Gizzi, University of Stuttgart, Germany

                Reviewed by: Diane L. Damiano, National Institutes of Health (NIH), United States; Anitha Manohar, Merck, United States

                *Correspondence: Yury Ivanenko, y.ivanenko@ 123456hsantalucia.it

                This article was submitted to Bionics and Biomimetics, a section of the journal Frontiers in Bioengineering and Biotechnology

                Article
                10.3389/fbioe.2020.00998
                7462003
                32974319
                3daecb7b-350c-4901-ae28-f119b213b78b
                Copyright © 2020 Cappellini, Sylos-Labini, Dewolf, Solopova, Morelli, Lacquaniti and Ivanenko.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 25 May 2020
                : 30 July 2020
                Page count
                Figures: 6, Tables: 0, Equations: 0, References: 212, Pages: 17, Words: 0
                Categories
                Bioengineering and Biotechnology
                Review

                cerebral palsy,abnormal development,early development of locomotion,neuromuscular pattern generation,spinal locomotor output,rehabilitation

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