Axonal Synapses Utilize Multiple Synaptic Ribbons in the Mammalian Retina

Abstract

In the mammalian retina, bipolar cells and ganglion cells which stratify in sublamina a of the inner plexiform layer (IPL) show OFF responses to light stimuli while those that stratify in sublamina b show ON responses. This functional relationship between anatomy and physiology is a key principle of retinal organization. However, there are at least three types of retinal neurons, including intrinsically photosensitive retinal ganglion cells (ipRGCs) and dopaminergic amacrine cells, which violate this principle. These cell types have light-driven ON responses, but their dendrites mainly stratify in sublamina a of the IPL, the OFF sublayer. Recent anatomical studies suggested that certain ON cone bipolar cells make axonal or ectopic synapses as they descend through sublamina a, thus providing ON input to cells which stratify in the OFF sublayer. Using immunoelectron microscopy with 3-dimensional reconstruction, we have identified axonal synapses of ON cone bipolar cells in the rabbit retina. Ten calbindin ON cone bipolar axons made en passant ribbon synapses onto amacrine or ganglion dendrites in sublamina a of the IPL. Compared to the ribbon synapses made by bipolar terminals, these axonal ribbon synapses were characterized by a broad postsynaptic element that appeared as a monad and by the presence of multiple short synaptic ribbons. These findings confirm that certain ON cone bipolar cells can provide ON input to amacrine and ganglion cells whose dendrites stratify in the OFF sublayer via axonal synapses. The monadic synapse with multiple ribbons may be a diagnostic feature of the ON cone bipolar axonal synapse in sublamina a. The presence of multiple ribbons and a broad postsynaptic density suggest these structures may be very efficient synapses. We also identified axonal inputs to ipRGCs with the architecture described above.

The M6 cell: A small‐field bistratified photosensitive retinal ganglion cell

“…This spectral behavior is typical of M5 ipRGCs (Stabio et al, 2018 cells. This raises the possibility that bipolar inputs to the outer arbor of M6 cells might be the target of the same unusual ON channel input as M1 ipRGCs and dopaminergic amacrine cells (Dumitrescu, Pucci, Wong, & Berson, 2009;Hoshi, Liu, Massey, & Mills, 2009;Kim et al, 2012). Among the targets of ectopic ON bipolar en passant synapses in rabbit retina are outer (distal) dendrites of the "bistratified diving cell" (Hoshi et al, 2009).…”

Balanced excitation and inhibition decorrelates visual feature representation in the mammalian inner retina

“…One central assumption was that BC axon terminals are the source of glutamate release in the IPL. However, some On BCs feature ectopic synapses along their axon (Dumitrescu et al, 2009;Kim et al, 2012) which might contribute to observed On responses in the Off sublamina ( Fig. 2d,g 2 ).…”

The morphological characterization of orientation‐biased displaced large‐field ganglion cells in the central part of goldfish retina

“…Recently, confocal analyses with an antibody to CtBP to label ribbon synapses revealed that ON‐type cone bipolar cells make ectopic synapses with the specific types of ganglion cells, such as melanopsin ganglion cells and dopaminergic amacrine cells in the rabbit and mouse retina at the stratum 1 of the IPL (Hoshi et al, ; Dumitrescu et al, ). More recent ultrastructural analyses have demonstrated that not only stratum 1, but more proximal parts of axonal processes of ON‐type cone bipolar cells also had multiple ectopic synaptic sites (Kim et al, ; Lauritzen et al, ). Furthermore, a calcium imaging study with SyGCaMP2 detected the ectopic signals in in vivo zebrafish retina (Dorostkar, Dreosti, Odermatt, & Lagnado, ).…”

“…Recently, specific types of ganglion or amacrine cells stratify into stratum 1 of the IPL receive ectopic synapses (van Haesendonck & Missotten, ; Hoshi, Liu, Massey, & Mills, ; Dumitrescu, Pucci, Wong, & Berson, ; Kim et al, ) or even more broadly in sublamina a (Lauritzen et al, ). Here, we show ectopic synapses from the Mb1 bipolar cell to this displaced ganglion cell that stratified into stratum 1 of the IPL.…”