title: Early functional impairment of sensory-motor connectivity in a mouse model of spinal muscular atrophy.
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.
authors.affiliation: Section on Developmental Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. gzmentis@columbia.edu
authors.forename: George Z
authors.initials: GZ
authors.lastname: Mentis
authors.forename: Dvir
authors.initials: D
authors.lastname: Blivis
authors.forename: Wenfang
authors.initials: W
authors.lastname: Liu
authors.forename: Estelle
authors.initials: E
authors.lastname: Drobac
authors.forename: Melissa E
authors.initials: ME
authors.lastname: Crowder
authors.forename: Lingling
authors.initials: L
authors.lastname: Kong
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Alvarez
authors.forename: Charlotte J
authors.initials: CJ
authors.lastname: Sumner
authors.forename: Michael J
authors.initials: MJ
authors.lastname: O'Donovan
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000473:pathology / Q000502:physiology*; D009134:Muscular Atrophy, Spinal / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D011984:Sensory Receptor Cells / Q000473:pathology / Q000502:physiology*; D013569:Synapses / Q000473:pathology / Q000502:physiology*