Multiple Invagination Patterns and Synaptic Efficacy in Primate and Mouse Rod Synaptic Terminals.

Purpose: Optical retina images are scaled based on eye size, which results in a linear scale ratio of 10:1 for human versus mouse and 7:1 for macaque monkey versus mouse. We examined how this scale difference correlates with the structural configuration of synaptic wiring in the rod spherule (RS) between macaque and mouse retinas compared with human data.

Methods: Rod bipolar cell (BC) dendrites and horizontal cell (HC) axonal processes, which invaginate the RS to form synaptic ribbon-associated triads, were examined by serial section transmission electron microscopy.

Helical Fasciculation of Bipolar and Horizontal Cell Neurites for Wiring With Photoreceptors in Macaque and Mouse Retinas.

Purpose: The three-dimensional configurations of rod and cone bipolar cell (BC) dendrites and horizontal cell (HC) processes outside rod and cone synaptic terminals have not been fully elucidated. We reveal how these neurites are mutually arranged to coordinate formation and maintenance of the postsynaptic complex of ribbon synapses in mouse and monkey retinas.

Methods: Serial section transmission electron microscopy was utilized to reconstruct BC and HC neurites in macaque monkey and mouse, including metabotropic glutamate receptor 6 (mGluR6)-knockout mice.

Classification of Mouse Retinal Bipolar Cells: Type-Specific Connectivity with Special Reference to Rod-Driven AII Amacrine Pathways.

We confirmed the classification of 15 morphological types of mouse bipolar cells by serial section transmission electron microscopy and characterized each type by identifying chemical synapses and gap junctions at axon terminals. Although whether the previous type 5 cells consist of two or three types was uncertain, they are here clustered into three types based on the vertical distribution of axonal ribbons. Next, while two groups of rod bipolar (RB) cells, RB1, and RB2, were previously proposed, we clarify that a half of RB1 cells have the intermediate characteristics, suggesting that these two groups comprise a single RB type.

ON Bipolar Cells in Macaque Retina: Type-Specific Synaptic Connectivity with Special Reference to OFF Counterparts.

To date, 12 macaque bipolar cell types have been described. This list includes all morphology types first outlined by Polyak (1941) using the Golgi method in the primate retina and subsequently identified by other researchers using electron microscopy (EM) combined with the Golgi method, serial section transmission EM (SSTEM), and immunohistochemical imaging. We used SSTEM for the rod-dense perifoveal area of macaque retina, reconfirmed ON (cone) bipolar cells to be classified as invaginating midget bipolar (IMB), diffuse bipolar (DB)4, DB5, DB6, giant bipolar (GB), and blue bipolar (BB) types, and clarified their type-specific connectivity.

Corrigendum: (1) Some OFF Bipolar Cell Types Make Contact With Both Rods and Cones in Macaque and Mouse Retinas; (2) OFF Bipolar Cells in Macaque Retina: Type-specific Connectivity in the Outer and Inner Synaptic Layers.

[This corrects the article on p. 105 in vol. 8, PMID: 25309346.

OFF bipolar cells in macaque retina: type-specific connectivity in the outer and inner synaptic layers.

OFF bipolar cells in the macaque retina were recently classified into five types: flat midget bipolar (FMB) and diffuse bipolar (DB) 1, 2, 3a, and 3b. We examined all parallel pathways from cone photoreceptors via OFF bipolar cells to parasol and midget ganglion cells by serial section transmission electron microscopy. Basal contacts of OFF bipolar cells to cone pedicles were previously categorized as triad-associated (TA) and non-TA (NTA).

Some OFF bipolar cell types make contact with both rods and cones in macaque and mouse retinas.

This study compared the types of OFF bipolar cells found in the macaque retina with those found in the mouse retina and determined whether these OFF bipolar cells make direct contacts with both rods and cones by serial section transmission electron microscopy. We performed scatter plots and cluster analysis of the morphological variables of their axon terminals such as the stratification level, the arbor thickness, the arbor area, and the number of ribbons. Five OFF bipolar cell types, including the recently discovered DB3b type, were identified in the macaque retina.

Effects of mGluR6-deficiency on photoreceptor ribbon synapse formation: comparison of electron microscopic analysis of serial sections with random sections.

This study examined the effects of metabotropic glutamate receptor 6 (mGluR6) deficiency on ribbon synapse formation in rod spherules and cone pedicles using serial-section electron microscopy. In a wild-type (WT) mouse, only 3% of spherules had one invaginating bipolar dendrite (1B-type) and 97% of spherules were 2B-type. In contrast, in an mGluR6-knockout (KO) mouse, 29% of spherules were 1B-type and 71% of spherules were 2B-type.

Functional allocation of synaptic contacts in microcircuits from rods via rod bipolar to AII amacrine cells in the mouse retina.

Retinal microcircuits for night vision at the absolute threshold are required to relay a single-photon rod signal reliably to ganglion cells via rod bipolar (RB) cells and AII amacrine cells. To assess the noise reduction of intercellular signal transmission in this rod-specific pathway, we quantified its synaptic connectivity by 3D reconstruction of a series of electron micrographs. In most cases (94%), each rod made ribbon synaptic contacts onto two adjacent RB cells.

Formation of a disulfide protein conjugate of the SH-group-containing metabolite (M-I) of esonarimod (KE-298) and its elimination in rats.

The reactivity of the thiol moiety of the active main metabolite (M-I) of esonarimod (KE-298), a novel anti-rheumatic agent, was investigated in rats. After repeated oral administration of 14C-KE-298, the radioactivity decreased rapidly and no tendency towards accumulation was found, in marked contrast to other common SH-group-containing drugs. At 30 min after intravenous administration of 14C-M-I to rats, the concentration of the 14C-M-I plasma protein conjugate in plasma was extremely low at 0.