AFFERENT INFLUENCES ON BRAIN-STEM AUDITORY NUCLEI OF THE CHICKEN - REGULATION OF TRANSCRIPTIONAL ACTIVITY FOLLOWING COCHLEA REMOVAL

Neuronal survival in the cochlear nucleus of young animals is regulate d by afferent activity. Removal or blockade of nerve VIII input result s in the death of 20-40% of neurons in the cochlear nucleus, nucleus m agnocellularis (NM), of the 10-14 days posthatch chick. Neuronal death in NM is preceded by complete failure of protein synthesis and degrad ation of ribosomes. In addition, there is a biphasic change in the imm unoreactivity of ribosomes for a monoclonal antiribosomal RNA antibody , Y10B. Initially, the entire population of afferent-deprived NM neuro ns loses Y10B immunoreactivity, but, after 6 or 12 hours of afferent d eprivation, lack of Y10B immunoreactivity specifically marks dying NM neurons. Whether RNA synthesis is also altered in afferent-deprived NM neurons has not previously been studied. To determine whether RNA syn thesis in NM neurons is regulated by loss of afferent activity, we inj ected chicks with H-3-uridine following unilateral cochlea removal and measured the incorporation of RNA precursor with tissue autoradiograp hy. As early as 1 hour after cochlea removal, there was a significant decrease in H-3-uridine incorporation by afferent-deprived NM neurons. After longer periods of afferent deprivation (6 or 12 hours), the maj ority of dying NM neurons (marked by loss of Y10B immunoreactivity) fa il to incorporate RNA precursor. Six or 12 hours following cochlea rem oval, the subpopulation of surviving NM neurons incorporates 3H-uridin e at increased levels over those observed 1 or 3 hours after cochlea r emoval. These findings suggest that nuclear function is regulated by a fferent synaptic activity and that failure of RNA synthesis occurs ear ly in the cell death process. (C) 1995 Wiley-Liss, Inc.