Unified classification of mouse retinal ganglion cells using function, morphology, and gene expression

Goetz, Jillian J.; Jessen, Zachary F.; Jacobi, Anne; Mani, Adam; Cooler, Sam; Greer, Devon; Kadri, Sabah; Segal, Jeremy P.; Shekhar, Karthik; Sanes, Joshua R.; Schwartz, Gregory William

doi:10.1016/j.celrep.2022.111040

Cited by 100 publications

(127 citation statements)

References 76 publications

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“…When only a single one of these cadherins is deleted, ooDSGC phenotypes are quite mild – notably milder than the phenotype of Flrt2 and Unc5c single mutants (Duan et al, 2018). It is therefore possible that a more thorough disruption of the FLRT-UNC5-LPHN system would produce more profound phenotypes, particularly since Flrt3 is also expressed by a subset of DSGCs (Goetz et al, 2022; Ruff et al, 2021; Shekhar et al, 2022). Further work will be needed to test this possibility and thereby to assess the relative importance of the early vs. late laminar targeting systems.…”

Section: Discussionmentioning

confidence: 99%

Rejection of inappropriate synaptic partners mediated by transcellular FLRT2-UNC5 signaling

Prigge

Sharma

Dembla

et al. 2022

Preprint

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During nervous system development, neurons choose synaptic partners with remarkable specificity; however, the cell-cell recognition mechanisms governing rejection of inappropriate partners remain enigmatic. Here we show that mouse retinal neurons avoid inappropriate partners using the FLRT2-UNC5 receptor-ligand system. Within the inner plexiform layer (IPL), FLRT2 is expressed by direction-selective (DS) circuit neurons, whereas UNC5C/D are expressed by non-DS neurons projecting to adjacent IPL sublayers. In vivo gain- and loss-of-function experiments demonstrate that FLRT2-UNC5 binding eliminates growing DS dendrites that have strayed from the DS circuit IPL sublayers. Abrogation of FLRT2-UNC5 binding allows mistargeted arbors to persist, elaborate, and acquire synapses from inappropriate partners. Conversely, UNC5C misexpression within DS circuit sublayers inhibits dendrite growth and drives arbors into adjacent sublayers. Mechanistically, UNC5s promote dendrite elimination by interfering with FLRT2-mediated adhesion. Based on their broad expression, FLRT-UNC5 recognition is poised to exert widespread effects upon synaptic partner choices across the nervous system.

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Section: Discussionmentioning

confidence: 99%

Rejection of inappropriate synaptic partners mediated by transcellular FLRT2-UNC5 signaling

Prigge

Sharma

Dembla

et al. 2022

Preprint

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“…For simplicity, we refer to the lgfbp5-positive On RGCs in the following as transient On small (tOn-small) cells. Mouse transient On-alpha (tOn-α) RGCs stratify at the same level as the tOn-small cells, but have a slightly larger dendritic tree (Goetz et al, 2021) and are osteopontin-positive (Krieger et al, 2017). We think that the tON-small RGCs are homologous to primate parasol cells (Fig.…”

Section: Figure 2 | Igfbp5-positive Ton-small Ganglion Cells Differ M...mentioning

confidence: 97%

“…1D and 2A,C; Fig. 2-1C) were presumably On cells as they stratified in sublamina 3; their morphology resembled that of "6sn" (Bae et al, 2018), "ON transient small RF" (Goetz et al, 2021), cluster 2 (Kong et al, 2005), PV2 (Farrow et al, 2013), "cluster X" (Sümbül et al, 2014), and "inner" RGB3 cells (Sun et al, 2002). For simplicity, we refer to the lgfbp5-positive On RGCs in the following as transient On small (tOn-small) cells.…”

Section: Figure 2 | Igfbp5-positive Ton-small Ganglion Cells Differ M...mentioning

confidence: 97%

Spike desensitisation as a mechanism for high-contrast selectivity in retinal ganglion cells

Chang

Ran

Auferkorte

et al. 2022

Preprint

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In the vertebrate retina, several dozens of parallel channels relay information about the visual world to the brain. These channels are represented by the different types of retinal ganglion cells (RGCs), whose responses are rendered selective for distinct sets of visual features by various mechanisms. These mechanisms can be roughly grouped into synaptic interactions and cell-intrinsic mechanisms, with the latter including dendritic morphology as well as ion channel complement and distribution. Here, we investigate how strongly ion channel complement can shape RGC output by comparing two mouse RGC types, the well-described ON alpha cell and a little-studied ON cell that is EGFP-labelled in the Igfbp5 mouse line and displays an unusual selectivity for high-contrast stimuli. Using patch-clamp recordings and computational modelling we show that in ON Igfbp5 cells - but not in the ON alpha cells - a higher activation threshold and a pronounced slow inactivation of the voltage-gated Na+ channels are responsible for the distinct contrast tuning and transient responses of ON Igfbp5 RGCs, respectively. This study provides an example for the powerful role that the last stage of retinal processing can play in shaping RGC responses.

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“…RGCs consist of distinct subclasses of cells that are selectively activated by specific types of information through visual and non-visual pathways (Masland, 2012). As the output of the mammalian retina in the first stage of visual processing, RGCs consist of over 30 different types, which can be distinguished by their dendritic anatomies, response properties, or molecular markers (Baden et al, 2016;Bae et al, 2018;Goetz et al, 2022;Rheaume et al, 2018). Numerous electrophysiological explorations have been conducted to uncover functional properties of mouse RGCs.…”

Section: Introductionmentioning

confidence: 99%

Linking transcriptomes with morphological and functional phenotypes in mammalian retinal ganglion cells

Huang¹,

Xu²,

Su³

et al. 2022

Cell Reports

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Unified classification of mouse retinal ganglion cells using function, morphology, and gene expression

Cited by 100 publications

References 76 publications

Rejection of inappropriate synaptic partners mediated by transcellular FLRT2-UNC5 signaling

Rejection of inappropriate synaptic partners mediated by transcellular FLRT2-UNC5 signaling

Spike desensitisation as a mechanism for high-contrast selectivity in retinal ganglion cells

Linking transcriptomes with morphological and functional phenotypes in mammalian retinal ganglion cells

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