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Corinne Beier, Daniel V Palanker, Alexander Sher; Stereotyped synaptic connectivity is restored during circuit repair in the adult mammalian retina. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1875.
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© ARVO (1962-2015); The Authors (2016-present)
Proper function of the CNS depends on synaptic specificity, which is known to form during development. The potential for the adult mammalian CNS to reestablish synaptic specificity following injury or disease remains unknown. Here, we ask if the selective synaptic connectivity between S-cones and S-cone bipolar cells can be reestablished after circuit disruption in the adult mammalian retina.
Photoreceptors in a 100µm-wide area were ablated in vivo in the adult ground squirrel retina using selective laser photocoagulation. S-cone bipolar cells were assessed 1-week, 1, 2, or 4 -months post ablation with IHC (anti-HCN4, mGluR6, iGluR5, CtBP2, S-opsin).
S-cone bipolar cells create new dendritic branches in response to deafferentation and some cells, termed edge cells, extend their dendrites out of the ablation zone into photoreceptor-rich areas (n=145 edge cells from 10 lesions). While only 6% of photoreceptors are S-cones, the dendritic branches of 51% (n=74/145) of the edge cells terminate at an S-cone pedicle. These S-cones are significantly more likely to diverge to more than one S-cone bipolar cell (binomial, p<1e-7). Randomizing (by rotation) the cone mosaic with respect to the S-cone bipolar cell dendrites showed that S-cone pedicle encounters were random, but terminations at S-cones were not; only 20% of edge cells terminated at an S-cone pedicle after the cone mosaic transformation but, 52% of those edge cells encountered an S-cone pedicle. New dendritic terminations at S-cones resemble normal synapses. The overlap between mGluR6 and HCN4 at S-cone pedicles contacted by edge cells was consistent with divergent S-cones (t-test, p=0.92) in the healthy retina. Although dendrites pass, on average, two M-cones before synapsing to an S-cone, they rarely synapse with M-cones (n=4/23 edge cells). Despite successful synaptogenesis, S-cone bipolar cells do not prune their dendritic branches.
The new dendrites of deafferented S-cone bipolar cells, after a random search, make preferential synaptic contacts with S-cones, while bypassing the more populous M-cones. Thus, synaptic specificity can be established not only during development, but in the adult mammalian retina as well. Some aspects of circuit reassembly resemble developmental mechanisms (dendritic expansion and synaptic precision), but other developmental mechanisms are missing (dendrite refinement).
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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