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The Journal of Neuroscience, September 1, 2002, 22(17):7639-7649

Local and Target-Derived Brain-Derived Neurotrophic Factor Exert Opposing Effects on the Dendritic Arborization of Retinal Ganglion Cells In Vivo

Barbara Lom^{1, 2}, Jeffrey Cogen¹, Analiza Lontok Sanchez¹, Thuy Vu¹, and Susana Cohen-Cory¹

¹ Mental Retardation Research Center, Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, California 90095, and ² Department of Biology and Program in Neuroscience, Davidson College, Davidson, North Carolina 28035-7118

The dendritic and axonal arbors of developing retinal ganglion cells (RGCs) are exposed to two sources of BDNF: RGC dendrites are exposed to BDNF locally within the retina, and RGC axons are exposed to BDNF at the target, the optic tectum. Our previous studies demonstrated that increasing tectal BDNF levels promotes RGC axon terminal arborization, whereas increasing retinal BDNF levels inhibits RGC dendritic arborization. These results suggested that differential neurotrophic action at the axon versus dendrite might be responsible for the opposing effects of BDNF on RGC axonal versus dendritic arborization. To explore this possibility, we examined the effects of altering BDNF levels at the optic tectum on the elaboration of RGC dendritic arbors in the retina. Increasing tectal BDNF levels resulted in a significant increase in dendritic branching, whereas neutralizing endogenous tectal BDNF with function-blocking antibodies significantly decreased dendritic arbor complexity. Thus, RGC dendritic arbors react in opposing manners to retinal- versus tectal-derived BDNF. Alterations in retinal BDNF levels, however, did not affect axon terminal arborization. Thus, RGC dendritic arborization is controlled in a complementary manner by both local and target-derived sources of BDNF, whereas axon arborization is modulated solely by neurotrophic interactions at the target. Together, our results indicate that developing RGCs modulate dendritic arborization by integrating signals from discrete sources of BDNF in the eye and brain. Differential integration of spatially discrete neurotrophin signals within a single neuron may therefore finely tune afferent and efferent neuronal connectivity.

Key words: brain-derived neurotrophic factor; retinal ganglion cell; retina; dendrite; arborization; Xenopus laevis; visual system development; neurotrophin

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22177639-11$05.00/0

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