Afferent influences on brainstem auditory nuclei of the chicken: regulation of transcriptional activity following cochlea removal.

Neuronal survival in the cochlear nucleus of young animals is regulated by afferent activity. Removal or blockade of nerve VIII input results in the death of 20-40% of neurons in the cochlear nucleus, nucleus magnocellularis (NM), of the 10-14 days posthatch chick. Neuronal death in NM is preceded by complete failure of protein synthesis and degradation of ribosomes. In addition, there is a biphasic change in the immunoreactivity of ribosomes for a monoclonal antiribosomal RNA antibody, Y10B. Initially, the entire population of afferent-deprived NM neurons loses Y10B immunoreactivity, but, after 6 or 12 hours of afferent deprivation, 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 synthesis in NM neurons is regulated by loss of afferent activity, we injected chicks with 3H-uridine following unilateral cochlea removal and measured the incorporation of RNA precursor with tissue autoradiography. As early as 1 hour after cochlea removal, there was a significant decrease in 3H-uridine incorporation by afferent-deprived NM neurons. After longer periods of afferent deprivation (6 or 12 hours), the majority of dying NM neurons (marked by loss of Y10B immunoreactivity) fail to incorporate RNA precursor. Six or 12 hours following cochlea removal, the subpopulation of surviving NM neurons incorporates 3H-uridine at increased levels over those observed 1 or 3 hours after cochlea removal. These findings suggest that nuclear function is regulated by afferent synaptic activity and that failure of RNA synthesis occurs early in the cell death process.