title: Stochastic Interaction between Neural Activity and Molecular Cues in the Formation of Topographic Maps.
abstract: 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 knockin (Isl2(EphA3/+)) 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 Isl2(EphA3/+) 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.
authors.affiliation: Center for Integrative Neuroscience and Departments of Physiology and Bioengineering & Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Melinda T
authors.initials: MT
authors.lastname: Owens
authors.affiliation: Molecular, Cell & Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Feldheim
authors.affiliation: Center for Integrative Neuroscience and Departments of Physiology and Bioengineering & Therapeutic Sciences, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Stryker
authors.affiliation: Molecular, Cell & Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064, USA; Center for Neuroscience Research, Children's National Health System, Washington, DC 20010, USA. Electronic address: jtriplett@childrensnational.org.
authors.forename: Jason W
authors.initials: JW
authors.lastname: Triplett
mesh_terms: D000818:Animals; D001931:Brain Mapping / Q000379:methods*; D003463:Cues; D055879:Gene Knock-In Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000502:physiology*; D013269:Stochastic Processes; D013477:Superior Colliculi / Q000166:cytology / Q000502:physiology*; D014795:Visual Pathways / Q000166:cytology / Q000502:physiology*