Brain-Derived Neurotrophic Factor and TrkB Modulate Visual Experience-Dependent Refinement of Neuronal Pathways in Retina

Abstract

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 brainderived 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.

Receptive field center size decreases and firing properties mature in ON and OFF retinal ganglion cells after eye opening in the mouse

“…RGCs with dendrites in both the ON and OFF layers of the IPL in young retinas appeared to shift to a single IPL layer with development. That ON-OFF RGCs decrease after eye opening is evident by physiology and morphology in other studies as well (Cantrell et al 2010;Landi et al 2007;Liu et al 2007;Tian and Copenhagen 2003). Thus, some ON and OFF cells detected at P30 likely would not have been detected from the same retina at eye opening, when they were ON-OFF responsive.…”

“…This classification is when the RGC dendrites are viewed in the plane of the retina. These dendrites, however, are dynamic in the vertical plane, shifting layers within the IPL after eye opening (Liu et al 2007;Xu and Tian 2007).…”

Setting the Pace for Retinal Development: Environmental Enrichment Acts Through Insulin-Like Growth Factor 1 and Brain-Derived Neurotrophic Factor

“…1998), and BDNF signaling modulates maturation of TH-immunoreactive amacrine cells (Liu et al, 2007). Dopaminergic input has been suggested to contribute to RGC receptive field organization in animals (for review, see Witkovsky, 2004).…”

“…Dopaminergic amacrine cells express BDNF receptor TrkB and are sensitive to BDNF (Cellerino and Kohler, 1997;Cellerino et al, 1998;Lee et al, 2005;Liu et al, 2007;Loeliger et al, 2008). Dopamine levels in the retina affect RGC receptive fields (for review, see Witkovsky, 2004), possibly contributing to retinal spatial resolution.…”

Cre recombinase‐mediated gene deletion in layer 4 of murine sensory cortical areas

“…Its promoter and regulatory elements have been used to generate several Six3-cre transgenic mouse lines (Furuta et al, 2000). Many of these cre transgenes are able to mediate deletion of a floxed gene in the hypothalamus and the retina (Furuta et al, 2000;Liu et al, 2007). We found that one of the reported lines, #69 (termed Six3-cre#69 here), was also able to mediate gene deletion in layer 4 of sensory cortical areas.…”