Blockade of endogenous ligands of trkB inhibits formation of ocular dominance columns.
We have examined the hypothesis that the segregation of LGN axon terminals into ocular dominance (OD) patches in layer 4 of the visual cortex requires neurotrophins, acting as signals to modulate the pattern of synaptic connectivity. Neurotrophin receptor antagonists, composed of the extracellular domain of each member of the trk family of neurotrophin receptors fused to a human Fc domain, were infused directly into visual cortex during the peak phase of OD column formation. Infusion of trkB-IgG, which binds BDNF and NT-4/5, inhibited the formation of OD patches within layer 4, while trkA-IgG and trkC-IgG, which preferentially bind NGF and NT-3, respectively, had no effect. The autoradiographic labeling of LGN terminals in cortical layer 4 was reduced by trkB-IgG, in contrast with the increased labeling observed following NT-4/5 infusion. These data suggest that an endogenous ligand of trkB, normally present in limiting amounts within visual cortex, is necessary for the selective growth and remodeling of LGN axons into eye-specific patches.
Cabelli
R J
RJ
Department of Cell and Neurobiology, University of Southern California School of Medicine, Los Angeles 90033, USA.
Shelton
D L
DL
Segal
R A
RA
Shatz
C J
CJ
D001369:Axons / Q000187:drug effects*; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology*; D008024:Ligands; D009414:Nerve Growth Factors / Q000494:pharmacology; D020933:Neurotrophin 3; D011505:Protein-Tyrosine Kinases / Q000187:drug effects*; D014793:Visual Cortex / Q000187:drug effects*
D007074:Immunoglobulin G; D008024:Ligands; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D011505:Protein-Tyrosine Kinases