Primary innervation of the avian and mammalian cochlear nucleus.

The auditory nerve of birds and mammals exhibits differences and similarities, but given the millions of years since the two classes diverged from a common ancestor, the similarities are much more impressive than the differences. The avian nerve is simpler than that of mammals, but share many fundamental features including principles of development, structure, and physiological properties. Moreover, the available evidence shows that the human auditory nerve follows this same general organizational plan. Equally impressive are reports that homologous genes in worms, flies, and mice exert the same heredity influences in man. The clear implication is that animal studies will produce knowledge that has a direct bearing on the human condition.

Development of the specialized AMPA receptors of auditory neurons.

At maturity, the AMPA receptors of auditory neurons exhibit very rapid desensitization kinetics and high permeability to calcium, reflecting the predominance of GluR3 flop and GluR4 flop subunits and the paucity of GluR2. We used mRNA analysis and immunoblotting to contrast the development of AMPA receptor structure in the chick cochlear nucleus [nucleus magnocellularis (NM)] with that of the slowly desensitizing and calcium-impermeable AMPA receptors of brainstem motor neurons in the nucleus of the glossopharyngeal/vagal nerves. The relative abundance of transcripts for GluRs 1-4 changes substantially in auditory (but not motor) neurons after embryonic day (E)10, with large decreases in GluR2 and increases in GluR3 and GluR4. Relative to the motor neurons, NM neurons show a higher abundance of flop isoforms of GluRs 2-4 at E10, suggesting that auditory neurons are already biased toward expression of flop isoforms before the onset of synaptic function at E11. Immunoreactivities in NM show very distinct developmental patterns from E13 onward: GluR2 declines by >90%, GluR3 increases threefold, and GluR4 remains relatively constant. Our results show that there are a series of critical points during normal development, most occurring after the onset of function, when rapid changes in receptor structure (occurring via both transcriptional and post-transcriptional control mechanisms) produce the specialized AMPA receptor functions that enable auditory neurons to accurately encode acoustic information.