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Early alterations in the electrophysiological properties of rat spinal motoneurones following neonatal axotomy

Authors

  • George Z. Mentis,

    1. 1Division of Neuroscience and Mental Health, Department of Cellular & Molecular Neuroscience, Imperial College London, Fulham Palace Road, London W6 8RF, UK
    2. 2Section of Developmental Neurobiology, Building 35, Room 3C1010, NINDS, NIH, Bethesda, MD 20892, USA
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  • Eugenia Díaz,

    1. 1Division of Neuroscience and Mental Health, Department of Cellular & Molecular Neuroscience, Imperial College London, Fulham Palace Road, London W6 8RF, UK
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  • Linda B. Moran,

    1. 1Division of Neuroscience and Mental Health, Department of Cellular & Molecular Neuroscience, Imperial College London, Fulham Palace Road, London W6 8RF, UK
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  • Roberto Navarrete

    1. 1Division of Neuroscience and Mental Health, Department of Cellular & Molecular Neuroscience, Imperial College London, Fulham Palace Road, London W6 8RF, UK
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Corresponding author G. Z. Mentis: Laboratory of Neural Control, Building 35, Room 3C1010, NINDS, NIH, Bethesda, MD 20892, USA. Email: mentisg@ninds.nih.gov

Abstract

Early in development, motoneurones are critically dependent on their target muscles for survival and differentiation. Previous studies have shown that neonatal axotomy causes massive motoneurone death and abnormal function in the surviving motoneurones. We have investigated the electrophysiological and morphological properties of motoneurones innervating the flexor tibialis anterior (TA) muscle during the first week after a neonatal axotomy, at a time when the motoneurones would be either in the process of degeneration or attempting to reinnervate their target muscles. We found that a large number (∼75%) of TA motoneurones died within 3 weeks after neonatal axotomy. Intracellular recordings revealed a marked increase in motoneurone excitability, as indicated by changes in passive and active membrane electrical properties. These changes were associated with a shift in the motoneurone firing pattern from a predominantly phasic pattern to a tonic pattern. Morphologically, the dendritic tree of the physiologically characterized axotomized cells was significantly reduced compared with age-matched normal motoneurones. These data demonstrate that motoneurone electrical properties are profoundly altered shortly after neonatal axotomy. In a subpopulation of the axotomized cells, abnormally high motoneurone excitability (input resistance significantly higher compared with control cells) was associated with a severe truncation of the dendritic arbor, suggesting that this excitability may represent an early electrophysiological correlate of motoneurone degeneration.

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