Figure 1.

Auditory neurons and their degeneration patterns. (A) The auditory nerve is a bundle of bipolar auditory neurons. The peripheral processes of auditory neurons form synapses with HCs and the central processes with CNs in the brainstem. HCs provide much of the trophic support required for the maintenance and survival of auditory neurons, including BDNF and NT-3. Auditory neurons synthesize the high-affinity tyrosine receptor kinases, TrkB and TrkC. The interface between the PNS and CNS is called the TZ, which is distal to the IAM. Myelin sheaths are formed by oligodendrocytes centrally from the TZ, and the surrounding milieu is astrocytic. Peripheral to the TZ, the myelin sheaths are formed by Schwann cells that are enveloped in endoneurium. The interface is penetrated only by axons. (B) The onset of anterograde (Wallerian) (૜), trans-neuronal (૝), and retrograde degeneration (૞) of the auditory nerve depends on the initial site of injury (x). In HC damage, neurodegeneration involves the auditory neuron entirely (૟) and neurodegeneration proceeds to higher-level neurons including the CNs (૝). Shaded arrows indicate the progression of degeneration, and dotted arrows indicate transneuronal degeneration. BDNF, brain-derived neurotrophic factor; CNS, central nervous system; CNs, cochlear nucleus cells; HC, hair cells; IAM, internal auditory meatus; NT-3, neurotrophin 3; PNS, peripheral nervous system; TZ, transitional zone.