Stochastic Interaction between Neural Activity and Molecular Cues in the Formation of Topographic Maps

Abstract

SUMMARY Topographic maps in visual processing areas maintain the spatial order of the visual world. Molecular cues and neuronal activity both play critical roles in map formation, but their interaction remains unclear. Here, we demonstrate that when molecular- and activity-dependent cues are rendered nearly equal in force, they drive topographic mapping stochastically. The functional and anatomical representation of azimuth in the superior colliculus of heterozygous Islet2-EphA3 knock-in (Isl2EphA3/+) mice is variable: maps may be single, duplicated, or a combination of the two. This heterogeneity is not due to genetic differences, since map organizations in individual mutant animals often differ between colliculi. Disruption of spontaneous waves of retinal activity resulted in uniform map organization in Isl2EphA3/+ mice, demonstrating that correlated spontaneous activity is required for map heterogeneity. Computational modeling replicates this heterogeneity, revealing that molecular- and activity-dependent forces interact simultaneously and stochastically during topographic map formation.

Superior Colliculus Does Play Dice

“…Yet, in this issue of Neuron, Owens et al (2015) identify stochastic interactions of molecular and activity-dependent forces that can produce heterogeneous retinocollicular maps.…”

“…To produce topographic maps, nearby neurons in an input region need to connect to nearby neurons in a target region. How developing neurons establish such spatially ordered connectivity, particularly when targets are far away and intervening axons disorganized, is an intriguing question, addressed by Owens et al (2015) for projections from the retina to superior colliculus (SC).…”

“…In this issue of Neuron, Owens et al (2015) examine how RGC axons achieve ordered distributions along the A-P axis of SC. This projection has long served as a model system for studies of topographic mapping (Cang and Feldheim, 2013).…”

“…In this issue of Neuron, Owens et al (2015) provide empirical and modeling evidence to suggest that topographic mapping of RGC axons instead emerges from a stochastic sorting process driven by relative EphA/ephrin-A signaling levels and spontaneous activity patterns. The authors use intrinsic signal imaging to analyze functional maps of visual space in SCs of wild-type (or Isl2 +/+ ), Isl2 EphA/+ , and Isl2 EphA/EphA mice.…”

“…To test whether the apparent discrepancy reflects differences in the sensitivity of functional and anatomical assays or may be caused by small sample sizes of previous studies, Owens et al (2015) correlate functional imaging and anatomical tracings in a larger cohort of Isl2 EphA/+ mice. The tracing experiments reveal that axons from nasal RGCs form heterogeneous termination zones in Isl2 EphA/+ mice: the majority are split in two (similar to previous observations), but a significant fraction are single.…”