Early Functional Impairment of Sensory-Motor Connectivity in a Mouse Model of Spinal Muscular Atrophy

George Z. Mentis, Dvir Blivis, Wenfang Liu, Estelle Drobac, Melissa E. Crowder, Lingling Kong, Francisco J. Alvarez, Charlotte J. Sumner, Michael J. O'Donovan

Research output: Contribution to journalArticle

Abstract

To define alterations of neuronal connectivity that occur during motor neuron degeneration, we characterized the function and structure of spinal circuitry in spinal muscular atrophy (SMA) model mice. SMA motor neurons show reduced proprioceptive reflexes that correlate with decreased number and function of synapses on motor neuron somata and proximal dendrites. These abnormalities occur at an early stage of disease in motor neurons innervating proximal hindlimb muscles and medial motor neurons innervating axial muscles, but only at end-stage disease in motor neurons innervating distal hindlimb muscles. Motor neuron loss follows afferent synapse loss with the same temporal and topographical pattern. Trichostatin A, which improves motor behavior and survival of SMA mice, partially restores spinal reflexes, illustrating the reversibility of these synaptic defects. Deafferentation of motor neurons is an early event in SMA and may be a primary cause of motor dysfunction that is amenable to therapeutic intervention.

Original languageEnglish (US)
Pages (from-to)453-467
Number of pages15
JournalNeuron
Volume69
Issue number3
DOIs
StatePublished - Feb 10 2011

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ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Mentis, G. Z., Blivis, D., Liu, W., Drobac, E., Crowder, M. E., Kong, L., Alvarez, F. J., Sumner, C. J., & O'Donovan, M. J. (2011). Early Functional Impairment of Sensory-Motor Connectivity in a Mouse Model of Spinal Muscular Atrophy. Neuron, 69(3), 453-467. https://doi.org/10.1016/j.neuron.2010.12.032