title: The anterogradely transported BDNF promotes retinal axon remodeling during eye specific segregation within the LGN.
abstract: Neurotrophins have been implicated in regulating many aspects of neuronal development and plasticity, including dendritic and axonal elaboration, by acting primarily as target derived trophic factors. Recently, we have shown that brain-derived neurotrophic factor (BDNF) is produced by retinal ganglion cells (RGCs) and travels in an anterograde direction along the optic nerve in neonatal rats. Here, we have assessed whether the anterogradely transported BDNF plays a role in shaping the retinogeniculate connectivity during development. We used intraocular injections of antisense oligonucleotides to suppress selectively retinal synthesis and anterograde transport of BDNF in rat pups. We found that in the absence of endogenous BDNF, RGC axons retract from their target in the dorsal lateral geniculate nucleus (dLGN). The blockade of BDNF action at the retinal level with the tyrosine kinase inhibitor, K252a, failed to produce this effect, suggesting an anterograde action of the endogenous BDNF. Moreover, the effects of BDNF removal on RGC fibers were evident only during a narrow temporal window coincident with the critical period for the retinothalamic refinement, indicating a role for BDNF on growth and elaboration of RGC axons rather than on their maintenance. Altogether these results propose a novel role for BDNF in the elaboration of retinogeniculate axons.
authors.affiliation: Scuola Normale Superiore, Piazza dei Cavalieri, 7-56100, Pisa, Italy. menna@in.cnr.it
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Menna
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Cenni
authors.forename: Sibel
authors.initials: S
authors.lastname: Naska
authors.forename: Lamberto
authors.initials: L
authors.lastname: Maffei
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000235:genetics; D005123:Eye / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D005829:Geniculate Bodies / Q000254:growth & development / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D012160:Retina / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D016376:Oligonucleotides, Antisense