The long-term objective of this program is an understanding, at the cellular level, of mechanisms involved in recovery from neural injury. This proposal is directed to the role of target innervation in recovery of spinal functions of injured peripheral nerves: specifically, of axotomized motor and sensory neurons of the cat's hindlimb. The general hypothesis to be tested is that innervation of an appropriate target enables recovery of spinal functions of axotomized motor and sensory nerves. Following nerve injury, regenerating sensory fibers may innervate foreign receptors (e.g., a muscle spindle afferent may innervate a tendon organ). Among possible central (i.e., spinal cord) consequences of such foreign innervation are (i) persistence of the afferent's original (now inappropriate) synaptic connections and actions, (ii) modification of central synaptic actions to bring accord with peripheral innervation, and (iii) decline of central synaptic actions. Muscle and cutaneous nerves will be cross- connected, giving regenerating muscle and cutaneous afferents foreign receptors as targets for reinnervation. In electrophysiological experiments, the central synaptic actions of these cross-connected afferents will be tested and compared with those of unoperated afferents, and of afferents which have (i) been cut and ligated or (ii) reinnervated their native or (iii) similar tissue. Two specific hypotheses concerning target requirements will be tested: (i) that afferents do not require receptor innervation to maintain their normal spinal function, and (ii) that receptor innervation is required, but there is latitude in the specific requirements (e.g., foreign receptors may suffice). Similarly, regenerating motor axons may innervate foreign muscle. When medial gastrocnemius motoneurons regenerate into soleus muscle, many of the MG motoneurons fail to recover their normal electrical properties, and they appear as though still axotomized. Cross-innervation, nerve-block and kinesiological experiments will test the specific hypotheses that (i) muscle-derived factors acquired during activity of the neuromuscular synapse permit motoneurons to recover from axotomy, and (ii) motoneurons which fail to recover normal electrical properties following muscle reinnervation fail also to recover normal functional properties. These experiments will provide direct, useful information concerning mechanisms and consequences of neural injury, and on regeneration and recovery of function.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS015913-12
Application #
3396554
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1979-12-01
Project End
1996-03-31
Budget Start
1992-04-01
Budget End
1993-03-31
Support Year
12
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of Florida
Department
Type
Schools of Medicine
DUNS #
073130411
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Mendell, L M; Munson, J B; Arvanian, V L (2001) Neurotrophins and synaptic plasticity in the mammalian spinal cord. J Physiol 533:91-7
Munson, J B; Johnson, R D; Mendell, L M (1999) Neurotrophin-3 and maintenance of muscle afferent function. Prog Brain Res 123:157-63
Gordon, T; Tyreman, N; Rafuse, V F et al. (1999) Limited plasticity of adult motor units conserves recruitment order and rate coding. Prog Brain Res 123:191-202
Mendell, L M; Johnson, R D; Munson, J B (1999) Neurotrophin modulation of the monosynaptic reflex after peripheral nerve transection. J Neurosci 19:3162-70
Munson, J B; McMahon, S B (1997) Effects of GDNF on axotomized sensory and motor neurons in adult rats. Eur J Neurosci 9:1126-9
Munson, J B; Foehring, R C; Mendell, L M et al. (1997) Fast-to-slow conversion following chronic low-frequency activation of medial gastrocnemius muscle in cats. II. Motoneuron properties. J Neurophysiol 77:2605-15
Taylor, J S; Friedman, R F; Munson, J B et al. (1997) Stretch hyperreflexia of triceps surae muscles in the conscious cat after dorsolateral spinal lesions. J Neurosci 17:5004-15
Munson, J B; Shelton, D L; McMahon, S B (1997) Adult mammalian sensory and motor neurons: roles of endogenous neurotrophins and rescue by exogenous neurotrophins after axotomy. J Neurosci 17:470-6
Gordon, T; Tyreman, N; Rafuse, V F et al. (1997) Fast-to-slow conversion following chronic low-frequency activation of medial gastrocnemius muscle in cats. I. Muscle and motor unit properties. J Neurophysiol 77:2585-604
Munson, J B; Johnson, R D; Mendell, L M (1997) NT-3 increases amplitude of EPSPs produced by axotomized group Ia afferents. J Neurophysiol 77:2209-12

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