Interplay of cell-autonomous and nonautonomous mechanisms tailors synaptic connectivity of converging axons in vivo.
Neurons receive input from diverse afferents but form stereotypic connections with each axon type to execute their precise functions. Developmental mechanisms that specify the connectivity of individual axons across populations of converging afferents are not well-understood. Here, we untangled the contributions of activity-dependent and independent interactions that regulate the connectivity of afferents providing major and minor input onto a neuron. Individual transmission-deficient retinal bipolar cells (BCs) reduced synapses with retinal ganglion cells (RGCs), but active BCs of the same type sharing the dendrite surprisingly did not compensate for this loss. Genetic ablation of some BC neighbors resulted in increased synaptogenesis by the remaining axons in a transmission-independent manner. Presence, but not transmission, of the major BC input also dissuades wiring with the minor input and with synaptically compatible but functionally mismatched afferents. Cell-autonomous, activity-dependent and nonautonomous, activity-independent mechanisms thus together tailor connectivity of individual axons among converging inner retinal afferents.
Department of Biological Structure, University of Washington, Seattle, WA 98195-7420, USA.
Haruhisa
H
Okawa
Department of Biological Structure, University of Washington, Seattle, WA 98195-7420, USA.
Luca
L
Della Santina
Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195-7290, USA; Howard Hughes Medical Institute, Seattle, WA 98195, USA.
Gregory W
GW
Schwartz
Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195-7290, USA; Howard Hughes Medical Institute, Seattle, WA 98195, USA.
Fred
F
Rieke
Department of Biological Structure, University of Washington, Seattle, WA 98195-7420, USA. Electronic address: wongr2@uw.edu.
Rachel O L
RO
Wong
D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000502:physiology*; D002450:Cell Communication / Q000235:genetics / Q000502:physiology*; D000076122:Disks Large Homolog 4 Protein; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D051528:Guanylate Kinases / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics; D008565:Membrane Proteins / Q000378:metabolism; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009415:Nerve Net / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000172:deficiency / Q000378:metabolism; D012160:Retina / Q000166:cytology; D051245:Retinal Bipolar Cells / Q000166:cytology / Q000502:physiology*; D013569:Synapses / Q000378:metabolism*; D013744:Tetanus Toxin / Q000235:genetics / Q000378:metabolism; D050988:Vesicle-Associated Membrane Protein 2 / Q000378:metabolism; D014795:Visual Pathways / Q000502:physiology
D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D008164:Luminescent Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D018094:Receptors, Metabotropic Glutamate; D013744:Tetanus Toxin; D050988:Vesicle-Associated Membrane Protein 2; C113897:metabotropic glutamate receptor 6; C494808:vesicle-associated membrane protein 2, mouse; D051528:Guanylate Kinases; D008666:Metalloendopeptidases; C093556:zinc-endopeptidase, tetanus neurotoxin