On the Achilles' heel of retinal ganglion cells: A physiological and modeling study of the thin axonal segment

Purpose. To analyze the structure and function of the thin axonal segment described in retinal ganglion cells. Methods. Whole-cell recordings from retinal ganglion cells were obtained in a superfused retina-eyecup preparation of the mudpuppy or tiger salamander, combined with antidromic stimulation of the optic nerve. Morphological studies of axons were based on intracellular staining and retrograde labeling techniques, including the use of confocal microscopy to view axons in situ. Computer modeling analysis was based on compartmental representations of realistic dendritic trees and equivalent cylinder models of ganglion cells; six different ion channels (five non-linear and 1 leakage channel) were used to model repetitive firing in ganglion cells. Results. In most ganglion cells, the axon begins at the soma with a relatively large axon hillock, which tapers to a very thing segment of 0.1 to 0.3 μm diameter and 35 to 130 μm in length, then increasing in diameter. Physiological recordings from ganglion cell somas reveal large amplitude, antidromic spikes, indicating that the thin segments must propagate impulses. Modeling studies clearly indicate that the thin segment must have a high density of Na channels to provide safety for impulse propagation in both ortho- and antidromic directions. When suitably large ion channel densities are placed in the thin segment, multiple zones of impulse initiation can occur and unique impulse encoding properties can result. Special encoding patterns are particularly evident to stimuli near threshold Conclusions. The thin axonal segment of retinal ganglion cells appears to play an important role in cell function and can have a major influence on impulse encoding behavior: its small size raises questions about cell vulnerability and toxicity.