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

Abstract

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.

Rhes travels from cell to cell and transports Huntington disease protein via TNT-like protrusion

“…Cell–cell communications, such as synaptic connections, gap junctions, and exosomes, are fundamental to living organisms (Lloyd and McIntyre, 1955; Farquhar and Palade, 1965; Johnstone et al, 1987; Beier et al, 2018; Cervera et al, 2018; Stahl and Raposo, 2018). The tunneling nanotubes (TNTs), the fragile and inconspicuous membranous tunnel-like structures ranging 50 to 200 nm in diameter and 5 to 125 µm in length connecting two cells, have been reported in diverse cell types (Rustom et al, 2004; Gerdes et al, 2007; Hase et al, 2009; Lou et al, 2012; Gousset et al, 2013; Schiller et al, 2013; Austefjord et al, 2014; Burtey et al, 2015; Polak et al, 2015; Wang and Gerdes, 2015; Delage et al, 2016; Desir et al, 2016; Zhu et al, 2016; Keller et al, 2017; Vignais et al, 2017; Dupont et al, 2018; Panasiuk et al, 2018).…”

Homeostatic plasticity in the retina is associated with maintenance of night vision during retinal degenerative disease

“…In contrast, recent evidence supports adaptive rather than solely destructive neural changes. For example, dendritic compensatory synapse formation occurs in retinal bipolar cells when various retinal cells, including rod and cone photoreceptors, have been ablated ( Beier et al, 2017 ; Beier et al, 2018 ; Care et al, 2019 ; Johnson et al, 2017 ; Shen et al, 2020 ). These studies suggested that rod or cone bipolar cell dendrites can extend their arbors and form new synapses with their correct targets (i.e.…”

Retinal glial remodeling by FGF21 preserves retinal function during photoreceptor degeneration

“…Rewiring cone-cone bipolar cells or potentiating rod-rod bipolar cell signaling preserves light responses in photoreceptor-degenerating mice ( Leinonen et al., 2020 ; Shen et al., 2020 ). Bipolar cells also participate in compensatory dendritic remodeling and synapse formation in response to the loss of photoreceptors ( Beier et al., 2017 , 2018 ; Care et al., 2019 ; Johnson et al., 2017 ; Shen et al., 2020 ). Therefore, modulating retinal remodeling in response to photoreceptor loss may help maintain or improve retinal function in response to retinal degeneration.…”