This application proposes a series of experimental neuroanatomical studies on the development of muscle spindles in the rat soleus muscle. It has three main objectives: 1) to examine the developmental mechanisms whereby spindles acquire the adult pattern of their sensory and motor neural connections; 2) to determine the role of sensory and motor neurons in the structural and histochemical differentiation of intrafusal fibers; and 3) to explore the mechanisms of the ontogenic effect of sensory neurons on spindle formation. Neural and muscular features of spindles in the soleus muscle will be compared by light and electron microscopy between developing and adult rats. In a complementary study, these features of developing spindles will also be compared between normal controls and animals subjected to experimental deafferentation and exposure to tetrodotoxin. These comparisons will be used to a) determine the temporal sequence of the development of sensory and motor innervation to spindles; b) establish whether transient, immature patterns of innervation procede the emergence of the adult pattern of neural connections of spindles; c) determine whether the motor innervation can direct the differentiation of developing spindles in the absence of sensory innervation; and d) explore whether nerve activity could mediate the ontogenetic effects of sensory axons on spindle formation. The proposed study aims at providing new insights into the process of formation and differentiation of mammalian muscle spindles. It will also explore nerve-muscle interactions during the development of a highly specialized class of muscle fibers - the intrafusal fibers of muscle spindles.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS025796-02
Application #
3411284
Study Section
Neurology B Subcommittee 1 (NEUB)
Project Start
1988-02-01
Project End
1991-01-31
Budget Start
1989-08-01
Budget End
1991-01-31
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Boston University
Department
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
Kucera, J; Fan, G; Walro, J et al. (1998) Neurotrophin-3 and trkC in muscle are non-essential for the development of mouse muscle spindles. Neuroreport 9:905-9
Wright, D E; Zhou, L; Kucera, J et al. (1997) Introduction of a neurotrophin-3 transgene into muscle selectively rescues proprioceptive neurons in mice lacking endogenous neurotrophin-3. Neuron 19:503-17
Kucera, J; Walro, J M (1995) An immunocytochemical marker for early type I muscle fibers in the developing rat hindlimb. Anat Embryol (Berl) 192:137-47
Ernfors, P; Kucera, J; Lee, K F et al. (1995) Studies on the physiological role of brain-derived neurotrophic factor and neurotrophin-3 in knockout mice. Int J Dev Biol 39:799-807
Kucera, J; Fan, G; Jaenisch, R et al. (1995) Dependence of developing group Ia afferents on neurotrophin-3. J Comp Neurol 363:307-20
Kucera, J; Ernfors, P; Walro, J et al. (1995) Reduction in the number of spinal motor neurons in neurotrophin-3-deficient mice. Neuroscience 69:321-30
Ernfors, P; Lee, K F; Kucera, J et al. (1994) Lack of neurotrophin-3 leads to deficiencies in the peripheral nervous system and loss of limb proprioceptive afferents. Cell 77:503-12
Kucera, J; Walro, J M (1994) Sequences of intrafusal fiber formation are muscle-dependent in rat hindlimbs. Anat Embryol (Berl) 190:273-86
Kucera, J; Walro, J M; Gao, Y (1993) Fusimotor-free spindles in reinnervated muscles of neonatal rats treated with nerve growth factor. Neuroscience 52:219-28
Kucera, J; Walro, J M (1993) Transient expression of a slow-tonic MHC isoform by extrafusal fibers in the developing rat. Anat Embryol (Berl) 188:409-18

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