Neurotrophins have profound effects on the development and maintenance of neurons that compose the VIIIth cranial nerve. In the auditory division of the nerve, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) have been localized to the sensory epithelium, and their respective high-affinity tyrosine kinase receptors (TrkB and TrkC) are expressed within the neuronal population. By using a culture methodology that allows evaluation of single neurons, we determined that BDNF and neurotrophin-4 (NT-4), which both bind to the TrkB high-affinity receptor, greatly enhanced neuron survival above control cultures. NT-3, which acts via the TrkC high-affinity receptor, also increased survival, but to a lesser extent. By testing a variety of neurotrophin concentrations and combinations, we observed that simultaneous activation of the TrkB and TrkC receptors synergistically promoted neuron survival compared to cultures that contained either neurotrophin alone at the same total concentration. Antibody labeling showed that the high-affinity Trk receptors were localized predominantly to the neurons and not to the surrounding satellite cells; furthermore, TrkB- and TrkC-specific antibodies each labeled 100% of the cultured neurons. These results suggest that synergistic interactions between BDNF and NT-3 may be crucial for spiral ganglion neuron survival during the final stages of development.

The neurotrophins brain-derived neurotrophin (BDNF) and neurotrophin-3 (NT-3) synergistically enhance survival of spiral ganglion neurons such that simultaneous exposure to both compounds produces a larger response than would be expected from their individual effects. To elucidate the functional role of this neurotrophin interaction, we examined its temporal and cell-type specificity in vitro for both mouse and gerbil spiral ganglion neurons. Synergistic effects were transient; they were maximal within the first two postnatal days and declined during the first postnatal week. Both neurotrophins were, however, still efficacious at increasing cell survival. After postnatal day 10, the effects of coexposure to BDNF and NT-3 were additive rather than synergistic. Synergism declined more rapidly in mouse than gerbil neurons, reflecting the difference in cochlear development for each species. Only neurons without peripherin epitopes, putative type I neurons, showed synergistic survival effects; survival of peripherin-expressing neurons was purely additive. Therefore, during a restricted time period, identical neurotrophin stimuli are capable of preferentially enhancing survival of one class of neurons that compose approximately 95% of the adult spiral ganglion.

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The neurotrophins brain-derived neurotrophin (BDNF) and neurotrophin-3 (NT-3) synergistically enhance survival of spiral ganglion neurons such that simultaneous exposure to both compounds produces a larger response than would be expected from their individual effects. To elucidate the functional role of this neurotrophin interaction, we examined its temporal and cell-type specificity in vitro for both mouse and gerbil spiral ganglion neurons. Synergistic effects were transient; they were maximal within the first two postnatal days and declined during the first postnatal week. Both neurotrophins were, however, still efficacious at increasing cell survival. After postnatal day 10, the effects of coexposure to BDNF and NT-3 were additive rather than synergistic. Synergism declined more rapidly in mouse than gerbil neurons, reflecting the difference in cochlear development for each species. Only neurons without peripherin epitopes, putative type I neurons, showed synergistic survival effects; survival of peripherin-expressing neurons was purely additive. Therefore, during a restricted time period, identical neurotrophin stimuli are capable of preferentially enhancing survival of one class of neurons that compose approximately 95% of the adult spiral ganglion.