title: Mechanism for Selective Synaptic Wiring of Rod Photoreceptors into the Retinal Circuitry and Its Role in Vision.
abstract: In the retina, rod and cone photoreceptors form distinct connections with different classes of downstream bipolar cells. However, the molecular mechanisms responsible for their selective connectivity are unknown. Here we identify a cell-adhesion protein, ELFN1, to be essential for the formation of synapses between rods and rod ON-bipolar cells in the primary rod pathway. ELFN1 is expressed selectively in rods where it is targeted to the axonal terminals by the synaptic release machinery. At the synapse, ELFN1 binds in trans to mGluR6, the postsynaptic receptor on rod ON-bipolar cells. Elimination of ELFN1 in mice prevents the formation of synaptic contacts involving rods, but not cones, allowing a dissection of the contributions of primary and secondary rod pathways to retinal circuit function and vision. We conclude that ELFN1 is necessary for the selective wiring of rods into the primary rod pathway and is required for high sensitivity of vision.
authors.affiliation: Department of Neuroscience, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Neuroscience, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Sarria
authors.affiliation: Jules Stein Eye Institute, Department of Ophthalmology, University of California, Los Angeles, 100 Stein Plaza, Los Angeles, CA 90095, USA.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Fehlhaber
authors.affiliation: Electron Microscopy Core Facility, Max Planck Florida Institute, 1 Max Planck Way, Jupiter, FL 33458, USA.
authors.forename: Naomi
authors.initials: N
authors.lastname: Kamasawa
authors.affiliation: Department of Neuroscience, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA.
authors.forename: Cesare
authors.initials: C
authors.lastname: Orlandi
authors.affiliation: Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92121, USA.
authors.forename: Kiely N
authors.initials: KN
authors.lastname: James
authors.affiliation: Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92121, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Hazen
authors.affiliation: Department of Infectious Disease, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Gardner
authors.affiliation: Department of Infectious Disease, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Farzan
authors.affiliation: Department of Molecular Physiology and Biophysics, University of Iowa, 51 Newton Road, Iowa City, IA 52242, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, University of Iowa, 51 Newton Road, Iowa City, IA 52242, USA.
authors.forename: Sheila
authors.initials: S
authors.lastname: Baker
authors.affiliation: Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92121, USA.
authors.forename: Kristin
authors.initials: K
authors.lastname: Baldwin
authors.affiliation: Jules Stein Eye Institute, Department of Ophthalmology, University of California, Los Angeles, 100 Stein Plaza, Los Angeles, CA 90095, USA.
authors.forename: Alapakkam P
authors.initials: AP
authors.lastname: Sampath
authors.affiliation: Department of Neuroscience, The Scripps Research Institute, 130 Scripps Way, Jupiter, FL 33458, USA. Electronic address: kirill@scripps.edu.
authors.forename: Kirill A
authors.initials: KA
authors.lastname: Martemyanov
mesh_terms: D000818:Animals; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009415:Nerve Net / Q000502:physiology* / Q000648:ultrastructure; D010775:Photic Stimulation / Q000379:methods*; D051381:Rats; D012160:Retina / Q000502:physiology / Q000648:ultrastructure; D017948:Retinal Rod Photoreceptor Cells / Q000502:physiology* / Q000648:ultrastructure; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D014785:Vision, Ocular / Q000502:physiology*