title: Architecture and activity-mediated refinement of axonal projections from a mosaic of genetically identified retinal ganglion cells.
abstract: Our understanding of how mammalian sensory circuits are organized and develop has long been hindered by the lack of genetic markers of neurons with discrete functions. Here, we report a transgenic mouse selectively expressing GFP in a complete mosaic of transient OFF-alpha retinal ganglion cells (tOFF-alphaRGCs). This enabled us to relate the mosaic spacing, dendritic anatomy, and electrophysiology of these RGCs to their complete map of projections in the brain. We find that tOFF-alphaRGCs project exclusively to the superior colliculus (SC) and dorsal lateral geniculate nucleus and are restricted to a specific laminar depth within each of these targets. The axons of tOFF-alphaRGC are also organized into columns in the SC. Both laminar and columnar specificity develop through axon refinement. Disruption of cholinergic retinal waves prevents the emergence of columnar- but not laminar-specific tOFF-alphaRGC connections. Our findings reveal that in a genetically identified sensory map, spontaneous activity promotes synaptic specificity by segregating axons arising from RGCs of the same subtype.
authors.affiliation: Department of Neurobiology, Fairchild Science Building D235, Stanford University School of Medicine, Palo Alto, CA 94305, USA. adh1@stanford.edu
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Huberman
authors.forename: Mihai
authors.initials: M
authors.lastname: Manu
authors.forename: Selina M
authors.initials: SM
authors.lastname: Koch
authors.forename: Michael W
authors.initials: MW
authors.lastname: Susman
authors.forename: Amanda Brosius
authors.initials: AB
authors.lastname: Lutz
authors.forename: Erik M
authors.initials: EM
authors.lastname: Ullian
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Baccus
authors.forename: Ben A
authors.initials: BA
authors.lastname: Barres
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000378:metabolism*; D001931:Brain Mapping; D002772:Cholera Toxin / Q000235:genetics / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D005829:Geniculate Bodies / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007211:Indoles; D008564:Membrane Potentials / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D018408:Patch-Clamp Techniques / Q000379:methods; D011978:Receptors, Nicotinic / Q000172:deficiency; D012160:Retina / Q000166:cytology*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000502:physiology*; D013477:Superior Colliculi / Q000502:physiology*; D050494:Vesicular Acetylcholine Transport Proteins / Q000378:metabolism; D014795:Visual Pathways / Q000502:physiology
chemical_list: D002772:Cholera Toxin; D049452:Green Fluorescent Proteins; D007211:Indoles; D009419:Nerve Tissue Proteins; D011978:Receptors, Nicotinic; D050494:Vesicular Acetylcholine Transport Proteins; C493460:Slc18a3 protein, mouse; C007293:DAPI