Cone synapses in mammalian retinal rod bipolar cells

• Published in: Journal of comparative neurology (1911) 2018-08, Vol.526 (12), p.1896-1909
• Main Authors: Pang, Ji‐Jie, Yang, Zhuo, Jacoby, Roy A., Wu, Samuel M.
• Format: Article
• Language: English
• Subjects: Amacrine cells; Bipolar cells; Calbindin-D28K; cone synapse; confocal microscopy; Dendritic spines; immunohistology; Immunoreactivity; mGluR6 RRID: AB_784501; mouse; PKCα RRID: AB_477345; Postsynaptic density; Postsynaptic density‐95 RRID: AB_10807979; primate; Protein kinase C; Retina; rod bipolar cell; Rods; RRID: AB_2313718; RRID: AB_2650488; Synapses; synaptic vesicle protein RRID:AB_2315387; tracer injection
• ISSN: 0021-9967; 1096-9861
• DOI: 10.1002/cne.24456

Some mammalian rod bipolar cells (RBCs) can receive excitatory chemical synaptic inputs from both rods and cones (DBCR2), but anatomical evidence for mammalian cone‐RBC contacts has been sparse. We examined anatomical cone‐RBC contacts using neurobiotin (NB) to visualize individual mouse cones and standard immuno‐markers to identify RBCs, cone pedicles and synapses in mouse and baboon retinas. Peanut agglutinin (PNA) stained the basal membrane of all cone pedicles, and mouse cones were positive for red/green (R/G)‐opsin, whereas baboon cones were positive for calbindin D‐28k. All synapses in the outer plexiform layer were labeled for synaptic vesicle protein 2 (SV2) and PSD (postsynaptic density)‐95, and those that coincided with PNA resided closest to bipolar cell somas. Cone‐RBC synaptic contacts were identified by: (a) RBC dendrites deeply invaginating into the center of cone pedicles (invaginating synapses), (b) RBC dendritic spines intruding into the surface of cone pedicles (superficial synapses), and (c) PKCα immunoreactivity coinciding with synaptic marker SV2, PSD‐95, mGluR6, G protein beta 5 or PNA at cone pedicles. One RBC could form 0‐1 invaginating and 1‐3 superficial contacts with cones. 20.7% and 38.9% of mouse RBCs contacted cones in the peripheral and central retina (p  .05). In baboon retinas (n = 4 samples), cone‐RBC contacts involved 12.2% of RBCs (n = 416 cells) and 22.5% of cones (n = 225 cells). This suggests that rod and cone signals in the ON pathway are integrated in some RBCs before reaching AII amacrine cells. Using confocal microscopy combined with cellular and synaptic markers, the authors show that a subset of mouse and primate rod bipolar cells (RBCs) receives synapses from both cone and rod photoreceptors. These synapses allow such a novel subtype of rod bipolar cells to integrate rod and cone signals for better processing of mesopic light signals in the retinal ON pathway.