DEFINING RESPONSIVENESS OF AVIAN COCHLEAR NEURONS TO BRAIN-DERIVED NEUROTROPHIC FACTOR AND NERVE GROWTH-FACTOR BY HSV-1-MEDIATED GENE-TRANSFER

The importance of individual members of the neurotrophin gene family f or avian inner ear development is not clearly defined. Here we address the role of two neurotrophins, brain-derived neurotrophic factor (BDN F) and nerve growth factor (NGF), for innervation of the chicken cochl ea. We have used defective herpes simplex virus type 1 (HSV-1) vectors , or amplicons, to express these neurotrophins in dissociated cultures of cochlear neurons. HSV-l-mediated expression of BDNF promotes neuro nal survival similar to the maximal level seen by exogenously added BD NF and exceeds its potency to produce neurite outgrowth. In contrast, cochlear neurons transduced with an amplicon producing bioactive NGF s how no response. These results confirm BDNF as an important mediator o f neurotrophin signaling inside avian cochlear neurons. However, these neurons can be rendered NGF-responsive by transducing them with the h igh-affinity receptor for NGF, TrkA. This study underlines the usefuln ess of amplicons to study and modify neurotrophin signaling inside neu rons.