Hierarchical partner selection shapes rod-cone pathway specificity in the inner retina

Zhang, Chi; Hellevik, Ayana; Takeuchi, Shunsuke; Wong, Rachel

doi:10.1016/j.isci.2022.105032

Cited by 12 publications

(14 citation statements)

References 49 publications

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“…During the circuit assembly neurons must discriminate between many potential synaptic partners in a neuropil comprising densely intermingled processes of many different cell types. Our findings support the idea that the interactions between the vast number of CAMs expressed on the surfaces of neurons control a hierarchy of wiring decisions sequentially restricting the pool of possible targets 32,33 , The last step in this process is the selection of synaptic partners and this is determined by the relative preference between potential synaptic partners 34 .…”

Section: Discussionsupporting

confidence: 83%

Identifying determinants of synaptic specificity by integrating connectomes and transcriptomes

Yoo

Dombrovski

Mirshahidi

et al. 2023

Preprint

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How do developing neurons select their synaptic partners? To identify molecules matching synaptic partners, we integrated the synapse-level connectome of neural circuits with the developmental expression patterns and binding specificities of cell adhesion molecules (CAMs) on pre- and postsynaptic neurons. We focused on parallel synaptic pathways in the Drosophila visual system, in which closely related neurons form synapses onto closely related target neurons. We show that the choice of synaptic partners correlates with the matching expression of receptor-ligand pairs of Beat and Side proteins of the immunoglobulin superfamily (IgSF) CAMs. Genetic analysis demonstrates that these proteins determine the choice between alternative synaptic targets. Combining transcriptomes, connectomes, and protein interactome maps provides a framework to uncover the molecular logic of synaptic connectivity.

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Section: Discussionsupporting

confidence: 83%

Identifying determinants of synaptic specificity by integrating connectomes and transcriptomes

Yoo

Dombrovski

Mirshahidi

et al. 2023

Preprint

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“…S4), with no synapses with other BC types (n=7 cells). This synaptic specificity and the reciprocal synapse arrangement in RS ACs mirror those of mammalian A17 ACs 31 .…”

Section: Resultsmentioning

confidence: 60%

“…Whereas CBC axons directly synapse onto the retinal output neurons, retinal ganglion cells (RGCs), along with a plethora of amacrine cells (ACs), RBCs predominately form a ‘dyadic’ synapse with two types of inhibitory amacrine cells, small field A2 (or A-II) and large-field A17 ACs 15, 18, 19, 30 . The A17 AC almost exclusively makes reciprocal feedback synapses onto RBC axon terminals 31 . In contrast, A2 ACs receive numerous synapses from RBCs (∼40 synapses per RBC in mice), but do not provide feedback onto the RBCs 18, 32 .…”

Section: Introductionmentioning

confidence: 99%

Ancient origin of the rod bipolar cell pathway in the vertebrate retina

Hellevik,

Mardoum,

Hahn

et al. 2023

Preprint

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Vertebrates rely on rod photoreceptors for vision in low-light conditions1. Mammals have a specialized downstream circuit for rod signaling called the primary rod pathway, which comprises specific cell types and wiring patterns that are thought to be unique to this lineage2–6. Thus, it has been long assumed that the primary rod pathway evolved in mammals3, 5–7. Here, we challenge this view by demonstrating that the mammalian primary rod pathway is conserved in zebrafish, which diverged from extant mammals ∼400 million years ago. Using single-cell RNA-sequencing, we identified two bipolar cell (BC) types in zebrafish that are related to mammalian rod BCs (RBCs) of the primary rod pathway. By combining electrophysiology, histology, and ultrastructural reconstruction of the zebrafish RBCs, we found that, like mammalian RBCs8, both zebrafish RBC types connect with all rods and red-cones in their dendritic territory, and provide output largely onto amacrine cells. The wiring pattern of the amacrine cells post-synaptic to one RBC type is strikingly similar to that of mammalian RBCs, suggesting that the cell types and circuit design of the primary rod pathway have emerged before the divergence of teleost fish and amniotes (mammals, birds, reptiles). The second RBC type in zebrafish, which forms separate pathways from the first RBC type, is either lost in mammals or emerged in fish to serve yet unknown roles.Highlights-Zebrafish have two rod bipolar cell types (RBC1/2).-Synaptic connectivity of RBC1 resembles that of the mammalian RBCs.-The primary rod pathway therefore probably evolved more than 400 million years ago.-The second zebrafish RBC type, RBC2, forms a separate pathway from RBC1.

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“…In addition to contacting AII amacrine cells, rod bipolar cells also contact A17 and nNOS amacrine cells (55,56). And while A17 cells make most of their synapses onto rod bipolar cells, they also make occasional connections with cone bipolar cells (57). Furthermore, synapses from A17 cells onto bipolar cells involve GABA c receptors that may not have been fully blocked by picrotoxin used in most of our experiments, including those with Cx36 KO mice (58).…”

Section: Discussionmentioning

confidence: 94%

Using optogenetics to dissect rod inputs to OFF ganglion cells in the mouse retina

Sladek¹,

Thoreson²

2023

Front. Ophthalmol.

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IntroductionLight responses of rod photoreceptor cells traverse the retina through three pathways. The primary pathway involves synapses from rods to ON-type rod bipolar cells with OFF signals reaching retinal ganglion cells (RGCs) via sign-inverting glycinergic synapses. Secondly, rod signals can enter cones through gap junctions. Finally, rods can synapse directly onto cone OFF bipolar cells.MethodsTo analyze these pathways, we obtained whole cell recordings from OFF-type α RGCs in mouse retinas while expressing channelrhodopsin-2 in rods and/or cones.ResultsOptogenetic stimulation of rods or cones evoked large fast currents in OFF RGCs. Blocking the primary rod pathway with L-AP4 and/or strychnine reduced rod-driven optogenetic currents in OFF RGCs by ~1/3. Blocking kainate receptors of OFF cone bipolar cells suppressed both rod- and cone-driven optogenetic currents in OFF RGCs. Inhibiting gap junctions between rods and cones with mecloflenamic acid or quinpirole reduced rod-driven responses in OFF RGCs. Eliminating the exocytotic Ca2+ sensor, synaptotagmin 1 (Syt1), from cones abolished cone-driven optogenetic responses in RGCs. Rod-driven currents were not significantly reduced after isolating the secondary pathway by eliminating Syt1 and synaptotagmin 7 (Syt7) to block synaptic release from rods. Eliminating Syt1 from both rods and cones abolished responses to optogenetic stimulation. In Cx36 KO retinas lacking rod-cone gap junctions, optogenetic activation of rods evoked small and slow responses in most OFF RGCs suggesting rod signals reached them through an indirect pathway. Two OFF cells showed faster responses consistent with more direct input from cone OFF bipolar cells.DiscussionThese data show that the secondary rod pathway supports robust inputs into OFF α RGCs and suggests the tertiary pathway recruits both direct and indirect inputs.

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Hierarchical partner selection shapes rod-cone pathway specificity in the inner retina

Cited by 12 publications

References 49 publications

Identifying determinants of synaptic specificity by integrating connectomes and transcriptomes

Identifying determinants of synaptic specificity by integrating connectomes and transcriptomes

Ancient origin of the rod bipolar cell pathway in the vertebrate retina

Using optogenetics to dissect rod inputs to OFF ganglion cells in the mouse retina

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