Brain-derived neurotrophic factor and TrkB modulate visual experience-dependent refinement of neuronal pathways in retina.
Sensory experience refines neuronal structure and functionality. The visual system has proved to be a productive model system to study this plasticity. In the neonatal retina, the dendritic arbors of a large proportion of ganglion cells are diffuse in the inner plexiform layer. With maturation, many of these arbors become monolaminated. Visual deprivation suppresses this remodeling. Little is known of the molecular mechanisms controlling maturational and experience-dependent refinement. Here, we tested the hypothesis that brain-derived neurotrophic factor (BDNF), which is known to regulate dendritic branching and synaptic function in the brain, modulates the developmental and visual experience-dependent refinement of retinal ganglion cells. We used a transgenic mouse line, in which a small number of ganglion cells were labeled with yellow fluorescence protein, to delineate their dendritic structure in vivo. We found that transgenic overexpression of BDNF accelerated the laminar refinement of ganglion cell dendrites, whereas decreased TrkB expression or retina-specific deletion of TrkB, the cognate receptor for BDNF, retarded it. BDNF-TrkB signaling regulated the maturational formation of new branches in ON but not the bilaminated ON-OFF ganglion cells. Furthermore, BDNF overexpression overrides the requirement for visual inputs to stimulate laminar refinement and dendritic branching of ganglion cells. These experiments reveal a previously unrecognized action of BDNF and TrkB in controlling cell-specific, experience-dependent remodeling of neuronal structures in the visual system.
Liu
Xiaorong
X
Department of Ophthalmology, University of California, San Francisco, San Francisco, California 94143, USA.
Grishanin
Ruslan N
RN
Tolwani
Ravi J
RJ
Rentería
René C
RC
Xu
Baoji
B
Reichardt
Louis F
LF
Copenhagen
David R
DR
D000367:Age Factors; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D051381:Rats; D020813:Receptor, trkB / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D012160:Retina / Q000254:growth & development* / Q000378:metabolism* / Q000502:physiology; D012683:Sensory Deprivation / Q000502:physiology; D014785:Vision, Ocular / Q000502:physiology; D014795:Visual Pathways / Q000254:growth & development* / Q000378:metabolism* / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D020813:Receptor, trkB