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Abstract: BDNF signaling through its TrkB receptor plays a pivotal role in activity-dependent refinement of synaptic connectivity of retinal ganglion cells. Additionally, studies using TrkB knockout mice have suggested that BDNF/TrkB signaling is essential for the development of photoreceptors and for synaptic communication between photoreceptors and second order retinal neurons. Thus the action of BDNF on refinement of synaptic connectivity of retinal ganglion cells could be a direct effect in the inner retina, or it could be secondary to its proposed role in rod maturation and in the formation of rod to bipolar cell synaptic transmission. To address this matter we have conditionally eliminated TrkB within the retina. We find that rod function and synaptic transmission to bipolar cells is not compromised in these conditional knockout mice. Consistent with previous work, we find that inner retina neural development is regulated by retinal BDNF/TrkB signaling. Specifically we show here also that the complexity of neuronal processes of dopaminergic cells is reduced in conditional TrkB knockout mice. We conclude that retinal BDNF/TrkB signaling has its primary role in the development of inner retinal neuronal circuits, and that this action is not a secondary effect due to the loss of visual signaling in the outer retina. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]