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The Journal of Neuroscience, April 15, 1999, 19(8):3162-3170
Neurotrophin Modulation of the Monosynaptic Reflex after Peripheral Nerve Transection
Lorne M. Mendell1, Richard D. Johnson2, 3, and John B. Munson3 1 Department of Neurobiology and Behavior, State University of New York at Stony Brook, Stony Brook, New York 11794, 2 Department of Physiological Sciences,
College of Veterinary Medicine, and 3 Department of Neuroscience, College of Medicine, University of Florida, Gainesville, Florida 32610-0144 The effects of neurotrophin-3 (NT-3) and NT-4/5 on the function of axotomized group Ia afferents and motoneurons comprising the monosynaptic reflex pathway were investigated. The axotomized medial gastrocnemius (MG) nerve was provided with NT-3 or NT-4/5 for 8-35 d via an osmotic minipump attached to its central end at the time of axotomy. After this treatment, monosynaptic EPSPs were recorded intracellularly from MG or lateral gastrocnemius soleus (LGS) motoneurons in response to stimulation of the heteronymous nerve under pentobarbital anesthesia. Controls were preparations with axotomized nerves treated directly with vehicle; other axotomized controls were administered subcutaneous NT-3. Direct NT-3 administration (60 µg/d) not only prevented the decline in EPSP amplitude from axotomized afferents (stimulate MG, record LGS) observed in axotomy controls but, after 5 weeks, led to EPSPs larger than those from intact afferents. These central changes were paralleled by recovery of group I afferent conduction velocity. Removal of NT-3 4-5 weeks after beginning treatment resulted in a decline of conduction velocity and EPSP amplitude within 1 week to values characteristic of axotomy. The increased synaptic efficacy after NT-3 treatment was associated with enhanced connectivity of single afferents to motoneurons. NT-4/5 induced modest recovery in group I afferent conduction velocity but not of the EPSPs they elicited. NT-3 or NT-4/5 had no effect on the properties of treated motoneurons or their monosynaptic EPSPs. We conclude that NT-3, and to a limited extent NT-4/5, promotes recovery of axotomized group Ia afferents but not axotomized motoneurons or the synapses on them.
Key words: NT-3; NT-4/5; neurotrophin; motoneuron; motor neuron; muscle spindle; group Ia fiber; spinal cord; axotomy; EPSP
Copyright © 1999 Society for Neuroscience 0270-6474/99/1983162-09$05.00/0
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