Deafferented Adult Rod Bipolar Cells Create New Synapses with Photoreceptors to Restore Vision

Beier, Corinne; Հովհաննիսյան, Անահիտ; Weiser, Sydney; Kung, Jennifer; Lee, Seungjun; Lee, Dae Yeong; Huie, Philip; Dalal, Roopa; Palanker, Daniel; Sher, Alexander

doi:10.1523/jneurosci.2570-16.2017

Cited by 43 publications

(37 citation statements)

References 36 publications

(23 reference statements)

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“…In this study, we report that DSCAM acts in mature neurons to actively suppress dendrite growth, a novel mechanism to inhibit plasticity. Widespread ablation of photoreceptors has been shown to result in rod BC dendrite sprouting and innervation of rods located outside of the ablated region, helping to restore visual function in the ablated region (87). Surviving cone BCs, on the other hand, failed to sprout and innervate cones outside of the lesion (87).…”

Section: Discussionmentioning

confidence: 99%

DSCAM-mediated control of dendritic and axonal arbor outgrowth enforces tiling and inhibits synaptic plasticity

Simmons

Bloomsburg

Sukeena

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Mature mammalian neurons have a limited ability to extend neurites and make new synaptic connections, but the mechanisms that inhibit such plasticity remain poorly understood. Here, we report that OFF-type retinal bipolar cells in mice are an exception to this rule, as they form new anatomical connections within their tiled dendritic fields well after retinal maturity. The Down syndrome cell-adhesion molecule () confines these anatomical rearrangements within the normal tiled fields, as conditional deletion of the gene permits extension of dendrite and axon arbors beyond these borders. deletion in the mature retina results in expanded dendritic fields and increased cone photoreceptor contacts, demonstrating that DSCAM actively inhibits circuit-level plasticity. Electrophysiological recordings from OFF bipolar cells showed enlarged visual receptive fields, demonstrating that expanded dendritic territories comprise functional synapses. Our results identify cell-adhesion molecule-mediated inhibition as a regulator of circuit-level neuronal plasticity in the adult retina.

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Section: Discussionmentioning

confidence: 99%

DSCAM-mediated control of dendritic and axonal arbor outgrowth enforces tiling and inhibits synaptic plasticity

Simmons

Bloomsburg

Sukeena

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…The destruction of photoreceptors results in the disappearance of pre-synaptic photoreceptor ribbons and the post-synaptic markers, iGluR5 and metabotropic glutamate receptor 6 (mGluR6) (Figure 1E, F) [20]. One week after the ablation, the dendritic stalks of the deafferented S-cone bipolar cells appear to be undisturbed (Figure 1D) and their dendritic tips remain in the outer plexiform layer (OPL) (Figure 1C).…”

Section: Resultsmentioning

confidence: 99%

Stereotyped Synaptic Connectivity Is Restored during Circuit Repair in the Adult Mammalian Retina

2018

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Proper function of the central nervous system (CNS) depends on the specificity of synaptic connections between cells of various types. Cellular and molecular mechanisms responsible for the establishment and refinement of these connections during development are the subject of an active area of research [1-6]. However, it is unknown if the adult mammalian CNS can form new type-selective synapses following neural injury or disease. Here, we assess whether selective synaptic connections can be reestablished after circuit disruption in the adult mammalian retina. The stereotyped circuitry at the first synapse in the retina, as well as the relatively short distances new neurites must travel compared to other areas of the CNS, make the retina well suited to probing for synaptic specificity during circuit reassembly. Selective connections between short-wavelength sensitive cone photoreceptors (S-cones) and S-cone bipolar cells provides the foundation of the primordial blue-yellow vision, common to all mammals [7-18]. We take advantage of the ground squirrel retina, which has a one-to-one S-cone-to-S-cone-bipolar-cell connection, to test if this connectivity can be reestablished following local photoreceptor loss [8, 19]. We find that after in vivo selective photoreceptor ablation, deafferented S-cone bipolar cells expand their dendritic trees. The new dendrites randomly explore the proper synaptic layer, bypass medium-wavelength sensitive cone photoreceptors (M-cones), and selectively synapse with S-cones. However, non-connected dendrites are not pruned back to resemble unperturbed S-cone bipolar cells. We show, for the first time, that circuit repair in the adult mammalian retina can recreate stereotypic selective wiring.

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“…Loss of photoreceptor synapses, or impairment of their function in aging, causes rod bipolar cell dendrites to sprout as if searching for their lost partners [35–37]. To test whether sprouting is really a search strategy, Beier et al [38] made focal laser lesions in rabbit retina that selectively ablated photoreceptors but not bipolar cells. They then asked if deafferented bipolar cells would connect with spared photoreceptors surrounding the lesion.…”

Section: Late Plasticity Of Dendritesmentioning

confidence: 99%

“…Rod bipolars succeeded in doing so, partially restoring visual sensitivity. By contrast, cone bipolars could not, suggesting that there is cell-type specificity to the adult dendrite plasticity mechanisms [38]. As shown by the DSCAM work, however, cone bipolar dendrites have the potential to become plastic.…”

Section: Late Plasticity Of Dendritesmentioning

confidence: 99%

Dendrite morphogenesis from birth to adulthood

Prigge

Kay

2018

Current Opinion in Neurobiology

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Dendrites are the conduits for receiving (and in some cases transmitting) neural signals; their ability to do these jobs is a direct result of their morphology. Developmental patterning mechanisms are critical to ensuring concordance between dendritic form and function. This article reviews recent studies in vertebrate retina and brain that elucidate key strategies for dendrite functional maturation. Specific cellular and molecular signals control the initiation and elaboration of dendritic arbors, and facilitate integration of young neurons into particular circuits. In some cells, dendrite growth and remodeling continues into adulthood. Once formed, dendrites subdivide into compartments with distinct physiological properties that enable dendritic computations. Understanding these key stages of dendrite patterning will help reveal how circuit functional properties arise during development.

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Deafferented Adult Rod Bipolar Cells Create New Synapses with Photoreceptors to Restore Vision

Cited by 43 publications

References 36 publications

DSCAM-mediated control of dendritic and axonal arbor outgrowth enforces tiling and inhibits synaptic plasticity

DSCAM-mediated control of dendritic and axonal arbor outgrowth enforces tiling and inhibits synaptic plasticity

Stereotyped Synaptic Connectivity Is Restored during Circuit Repair in the Adult Mammalian Retina

Dendrite morphogenesis from birth to adulthood

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