Spontaneous Activity as a Determinant of Axonal Connections

To investigate the role of spontaneous retinal activity in map refinement, we studied goldfish kept in darkness during regeneration of a cut optic nerve. In one experiment, such fish (with lenses ablated to blur vision) were maintained for 70 days in stroboscopic light, diurnal light, or total darkness interrupted daily by 15 minutes of stroboscopic light. The retinotectal projection was then assessed for retinotopy by standard methods, using retrograde transport of wheat germ agglutinin-horseradish peroxidase. As in previous work, significantly more refinement was found in diurnal than in stroboscopic light. In darkness, refinement was as complete as in diurnal light. In a second experiment, similar fish were kept in stroboscopic light for 63 days. Some were then assessed to confirm that refinement had been delayed, while others were transferred to darkness or diurnal light for assessment later. After 7 days in either environment, no further refinement was seen; but after 21 days, substantial and significant refinement has occurred in both. Thus the effects of darkness and diurnal light were indistinguishable, and very different from those of stroboscopic light and (in previous studies) tetrodotoxin. Map refinement is evidently activity-dependent but not experience-dependent, and can effectively use the correlated spontaneous firing of neighbouring ganglion cells as its basis. Locally correlated spontaneous activity, which appears also to drive eye- and class-specific axon segregation in mammals, occurs widely in the nervous system. It could potentially generate systematic interconnection patterns even between neuronal populations without an overtly topographic organization.