title: Cell-autonomous TrkB signaling in presynaptic retinal ganglion cells mediates axon arbor growth and synapse maturation during the establishment of retinotectal synaptic connectivity.
abstract: BDNF contributes to the activity-dependent establishment and refinement of visual connectivity. In Xenopus, BDNF applications in the optic tectum influence retinal ganglion cell (RGC) axon branching and promote synapse formation and stabilization. The expression patterns of BDNF and TrkB suggest that BDNF specifically regulates the maturation of RGC axons at the target. It is possible, however, that BDNF modulates retinotectal synaptic connectivity by differentially influencing presynaptic RGC axons and postsynaptic tectal cells. Here, we combined single-cell expression of a dominant-negative TrkB-enhanced green fluorescent protein (GFP) fusion protein with confocal microscopy imaging in live Xenopus tadpoles to differentiate between presynaptic and postsynaptic actions of BDNF. Disruption of TrkB signaling in individual RGCs influenced the branching and synaptic maturation of presynaptic axon arbors. Specifically, GFP-TrkB.T1 overexpression increased the proportion of axons with immature, growth cone-like morphology, decreased axon branch stability, and increased axon arbor degeneration. In addition, GFP-TrkB.T1 overexpression reduced the number of red fluorescent protein-synaptobrevin-labeled presynaptic specializations per axon terminal. In contrast, overexpression of GFP-TrkB.T1 in tectal neurons did not alter synaptic number or the morphology or dynamic behavior of their dendritic arbors. Electron microscopy analysis revealed a significant decrease in the number of mature synaptic profiles and in the number of docked synaptic vesicles at retinotectal synapses made by RGC axons expressing GFP-TrkB.T1. Together, our results demonstrate that presynaptic TrkB signaling in RGCs is a key determinant in the establishment of visual connectivity and indicate that changes in tectal neuron synaptic connectivity are secondary to the BDNF-elicited enhanced stability and growth of presynaptic RGCs.
authors.affiliation: Department of Neurobiology and Behavior, University of California, Irvine, Irvine, California 92697, USA.
authors.forename: Sonya
authors.initials: S
authors.lastname: Marshak
authors.forename: Angeliki Maria
authors.initials: AM
authors.lastname: Nikolakopoulou
authors.forename: Ron
authors.initials: R
authors.lastname: Dirks
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Martens
authors.forename: Susana
authors.initials: S
authors.lastname: Cohen-Cory
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D003712:Dendrites / Q000502:physiology / Q000648:ultrastructure; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007814:Larva; D009410:Nerve Degeneration / Q000503:physiopathology; D017729:Presynaptic Terminals / Q000378:metabolism; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000502:physiology* / Q000648:ultrastructure; D012165:Retinal Ganglion Cells / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013477:Superior Colliculi / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D013569:Synapses / Q000502:physiology*; D014162:Transfection; D014795:Visual Pathways / Q000502:physiology; D014982:Xenopus laevis
chemical_list: D049452:Green Fluorescent Proteins; D020813:Receptor, trkB