title: The role of muscle spindles in the development of the monosynaptic stretch reflex.
abstract: Muscle sensory axons induce the development of specialized intrafusal muscle fibers in muscle spindles during development, but the role that the intrafusal fibers may play in the development of the central projections of these Ia sensory axons is unclear. In the present study, we assessed the influence of intrafusal fibers in muscle spindles on the formation of monosynaptic connections between Ia (muscle spindle) sensory axons and motoneurons (MNs) using two transgenic strains of mice. Deletion of the ErbB2 receptor from developing myotubes disrupts the formation of intrafusal muscle fibers and causes a nearly complete absence of functional synaptic connections between Ia axons and MNs. Monosynaptic connectivity can be fully restored by postnatal administration of neurotrophin-3 (NT-3), and the synaptic connections in NT-3-treated mice are as specific as in wild-type mice. Deletion of the Egr3 transcription factor also impairs the development of intrafusal muscle fibers and disrupts synaptic connectivity between Ia axons and MNs. Postnatal injections of NT-3 restore the normal strengths and specificity of Ia-motoneuronal connections in these mice as well. Severe deficits in intrafusal fiber development, therefore, do not disrupt the establishment of normal, selective patterns of connections between Ia axons and MNs, although these connections require the presence of NT-3, normally supplied by intrafusal fibers, to be functional.
authors.affiliation: Department of Molecular Physiology and Pharmacology, Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Wang
authors.forename: LingYing
authors.initials: L
authors.lastname: Li
authors.forename: Eric
authors.initials: E
authors.lastname: Frank
mesh_terms: D000199:Actins / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D004305:Dose-Response Relationship, Drug; D051776:Early Growth Response Protein 3 / Q000235:genetics; D004558:Electric Stimulation; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D009470:Muscle Spindles / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000502:physiology; D009414:Nerve Growth Factors / Q000494:pharmacology; D009475:Neurons, Afferent / Q000502:physiology; D011930:Reaction Time / Q000187:drug effects / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000172:deficiency; D012023:Reflex, Monosynaptic / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology; D055366:Synaptic Potentials / Q000187:drug effects / Q000235:genetics / Q000502:physiology
chemical_list: D000199:Actins; D051776:Early Growth Response Protein 3; D009414:Nerve Growth Factors; D018719:Erb-b2 Receptor Tyrosine Kinases; C497369:Egr3 protein, mouse; C518911:neurotropin 3, mouse; C524056:Erbb2 protein, mouse