title: Muscle spindle-derived neurotrophin 3 regulates synaptic connectivity between muscle sensory and motor neurons.
abstract: Ia afferents induce the formation of muscle spindles prenatally and maintain them postnatally. To address whether spindles, in turn, regulate the function of Ia afferents, we examined Egr3-null mutant mice (Egr3-/-), in which muscle spindles degenerate progressively after birth. Egr3-/- mice develop gait ataxia, scoliosis, resting tremors, and ptosis, suggesting a defect in proprioception. Despite the normal morphological appearance of peripheral and central sensory projections, we observed a profound functional deficit in the strength of sensory-motor connections in Egr3-/- mice. Muscle spindles in Egr3-/- mice do not express NT3. Intramuscular injections of NT3 to Egr3-/- mice during the postnatal period restored sensory-motor connections. Thus, NT3 derived from muscle spindles regulates the synaptic connectivity between muscle sensory and motor neurons.
authors.affiliation: Department of Neurobiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Hsiao-Huei
authors.initials: HH
authors.lastname: Chen
authors.forename: Warren G
authors.initials: WG
authors.lastname: Tourtellotte
authors.forename: Eric
authors.initials: E
authors.lastname: Frank
mesh_terms: D000200:Action Potentials; D000344:Afferent Pathways / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics; D018450:Disease Progression; D051776:Early Growth Response Protein 3; D004558:Electric Stimulation; D005071:Evoked Potentials; D066298:In Vitro Techniques; D007273:Injections, Intramuscular; D008161:Lumbosacral Region; D051379:Mice; D018345:Mice, Knockout; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D009470:Muscle Spindles / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000294:innervation / Q000473:pathology; D009475:Neurons, Afferent / Q000378:metabolism* / Q000473:pathology; D020933:Neurotrophin 3 / Q000008:administration & dosage / Q000378:metabolism*; D011930:Reaction Time; D020886:Somatosensory Disorders / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C497369:Egr3 protein, mouse; D020933:Neurotrophin 3; D014157:Transcription Factors; D051776:Early Growth Response Protein 3