Neurotrophin modulation of the monosynaptic reflex after peripheral nerve transection

The effects of neurotrophin-3 (NT-3) and NT-4/5 on the function of axotomiz ed group la afferents and motoneurons comprising the monosynaptic reflex pa thway 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 t o its central end at the time of axotomy. After this treatment. monosynapti c EPSPs were recorded intracellularly from MG or lateral gastrocnemius sole us (LGS) motoneurons in response to stimulation of the heteronymous nerve u nder pentobarbital anesthesia. Controls were preparations with axotomized n erves treated directly with vehicle; other axotomized controls were adminis tered subcutaneous NT-3. Direct NT-3 administration (60 mu g/d) not only pr evented the decline in EPSP amplitude from axotomized afferents (stimulate MG, record LGS) observed in axotomy controls but, after 5 weeks, led to EPS Ps larger than those from intact afferents. These central changes were para lleled by recovery of group I afferent conduction velocity. Removal of NT-3 4-5 weeks after beginning treatment resulted in a decline of conduction ve locity 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 mo dest 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 mo toneurons or their monosynaptic EPSPs. We conclude that NT-3, and to a limi ted extent NT-4/5, promotes recovery of axotomized group la afferents but n ot axotomized motoneurons or the synapses on them.