Multiple cell types form the VIP amacrine cell population

Müller, Luis Pérez de Sevilla; Solomon, Alexander; Sheets, Kristopher G.; Hapukino, Hinekura; Rodriguez, Allen; Brecha, Nicholas C.

doi:10.1002/cne.24234

Cited by 24 publications

(29 citation statements)

References 148 publications

(411 reference statements)

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“…To segregate cell types in the Vip-FlpO driver, we crossed it with the UBS-CreERT2 driver and achieved sparse labeling with a low dose of tamoxifen. The Vip-FlpO driver targeted FLPo expression in three AC types, consistent with the Cre expression pattern described in the Vip-Cre driver ( Akrouh and Kerschensteiner, 2015 ; Park et al, 2015 ; Perez de Sevilla Muller et al, 2017 ). The first type was a wide-field bistratified AC previously named VIP-1 ( Zhu et al, 2014 ; Akrouh and Kerschensteiner, 2015 ).…”

Section: Resultssupporting

confidence: 68%

Intersectional Strategies for Targeting Amacrine and Ganglion Cell Types in the Mouse Retina

Deniz

et al. 2018

Front. Neural Circuits

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The mammalian retina harbors over 100 different cell types. To understand how retinal circuits work, it is essential to systematically access each type. A widely used approach for achieving targeted transgene expression exploits promoter-driven Cre lines. However, Cre expression in a given transgenic line in the retina and elsewhere in the brain is rarely confined to a single cell type, contributing ambiguity to the interpretation of results from broadly applied manipulations. To obtain unambiguous information about retinal processing, it is desirable to have strategies for further restricting transgene expression to a few or even to a single cell type. We employed an intersectional strategy based on a Cre/Flp double recombinase system to target amacrine and ganglion cell types in the inner retina. We analyzed expression patterns in seven Flp drivers and then created combinational mouse lines by selective cross breeding with Cre drivers. Breeding with Flp drivers can routinely remove labeling from more than 90% of the cells in Cre drivers, leading to only a handful cell types, typically 2–3, remaining in the intersection. Cre/Flp combinatorial mouse lines enabled us to identify and anatomically characterize retinal cell types with greater ease and demonstrated the feasibility of intersectional strategies in retinal research. In addition to the retina, we examined Flp expression in the lateral geniculate nucleus and superior colliculus. Our results establish a foundation for future application of intersectional strategies in the retina and retino-recipient regions.

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Section: Resultssupporting

confidence: 68%

Intersectional Strategies for Targeting Amacrine and Ganglion Cell Types in the Mouse Retina

Deniz

et al. 2018

Front. Neural Circuits

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“…Previous electron microscopy reconstruction of cat β cells showed that inhibitory somatic contacts may originate from a single type of GABAergic AC (47). However, we show here that mouse ooDSGCs receive input onto their somata from two or more types of ACs, one of which resembles a bistratified VIP AC (37)(38)(39) and another that resembles the type 52 AC (40). Previous electrophysiological recordings from ooDSGCs in the absence of SAC GABAergic drive revealed the presence of sustained weaker and non-direction-selective inhibitory currents (23); these currents may reflect somatic inhibition, a possibility that remains to be tested.…”

Section: Discussioncontrasting

confidence: 49%

“…Because the type or types of ACs contacting ooDSGC somata are unknown, we reconstructed the ACs that synapsed onto the ooDSGCs (n = 4 cells), using a second SBFSEM dataset (36). We found that ooDSGCs are contacted by at least two types of ACs, one with morphology resembling bistratified VIP-expressing ACs (37)(38)(39) and the other with morphology resembling the type 52 AC of Helmstaedter et al (40) (Fig. 3 F-L and SI Appendix, Fig.…”

Section: Enlarged Somatic Yfpγ2 Puncta Colocalize With Other Inhibitorymentioning

confidence: 90%

GABA release selectively regulates synapse development at distinct inputs on direction-selective retinal ganglion cells

Bleckert

Zhang

Turner

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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Synaptic inhibition controls a neuron’s output via functionally distinct inputs at two subcellular compartments, the cell body and the dendrites. It is unclear whether the assembly of these distinct inhibitory inputs can be regulated independently by neurotransmission. In the mammalian retina, γ-aminobutyric acid (GABA) release from starburst amacrine cells (SACs) onto the dendrites of on–off direction-selective ganglion cells (ooDSGCs) is essential for directionally selective responses. We found that ooDSGCs also receive GABAergic input on their somata from other amacrine cells (ACs), including ACs containing the vasoactive intestinal peptide (VIP). When net GABAergic transmission is reduced, somatic, but not dendritic, GABAA receptor clusters on the ooDSGC increased in number and size. Correlative fluorescence imaging and serial electron microscopy revealed that these enlarged somatic receptor clusters are localized to synapses. By contrast, selectively blocking vesicular GABA release from either SACs or VIP ACs did not alter dendritic or somatic receptor distributions on the ooDSGCs, showing that neither SAC nor VIP AC GABA release alone is required for the development of inhibitory synapses in ooDSGCs. Furthermore, a reduction in net GABAergic transmission, but not a selective reduction from SACs, increased excitatory drive onto ooDSGCs. This increased excitation may drive a homeostatic increase in ooDSGC somatic GABAA receptors. Differential regulation of GABAA receptors on the ooDSGC’s soma and dendrites could facilitate homeostatic control of the ooDSGC’s output while enabling the assembly of the GABAergic connectivity underlying direction selectivity to be indifferent to altered transmission.

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“…al, 2011), VG3 ACs (C13: VGlut3 [Slc17a8]; Haverkamp and Wässle, 2004;Johnson et al, 2004;Krishnaswamy et al, 2015); and A17 ACs (C6: Prkca (PKCα), Sdk1, Calb2 negative, Dab1-negative; Grimes et al, 2010;Puthussery and Fletcher 2007;Yamagata and Sanes, 2019). Other types expressed neuropeptides known to mark specific AC types; they include Cck (C10,C17,C18,C34; Firth et al, 2002), Vip, (C22,C26,C47; Park et al, 2015;Akrouh and Kerschensteiner, 2015;Pérez de Sevilla Müller et al, 2019), Crh (C37; Park et al, 2018) and Penk (C35,C59,C63; Chen et al, 2013). For some of these types, we were able to validate new markers, such as Car3 for VG3 cells (Figure 3B,C).…”

Section: Correspondence Between Clusters and Ac Typesmentioning

confidence: 86%

Molecular identification of sixty-three amacrine cell types completes a mouse retinal cell atlas

Wang

et al. 2020

Preprint

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Amacrine cells (ACs) are a diverse class of interneurons that modulate input from photoreceptors to retinal ganglion cells (RGCs), rendering each RGC type selectively sensitive to particular visual features, which are then relayed to the brain. While many AC types have been identified morphologically and physiologically, they have not been comprehensively classified or molecularly characterized. We used high-throughput single-cell RNA sequencing (scRNA-seq) to profile >32,000 ACs from mouse retina, and applied computational methods to identify 63 AC types. We identified molecular markers for each type, and used them to characterize the morphology of multiple types. We show that they include nearly all previously known AC types as well as many that had not been described. Consistent with previous studies, most of the AC types express markers for the canonical inhibitory neurotransmitters GABA or glycine, but several express neither or both. In addition, many express one or more neuropeptides, and two express glutamatergic markers. We also explored transcriptomic relationships among AC types and identified transcription factors expressed by individual or multiple closely related types. Noteworthy among these were Meis2 and Tcf4, expressed by most GABAergic and most glycinergic types, respectively. Together, these results provide a foundation for developmental and functional studies of ACs, as well as means for genetically accessing them. Along with previous molecular, physiological and morphological analyses, they establish the existence of at least 130 neuronal types and nearly 140 cell types in mouse retina. SIGNIFICANCE STATEMENTThe mouse retina is a leading model for analyzing the development, structure, function and pathology of neural circuits. A complete molecular atlas of retinal cell types provides an important foundation for these studies. We used high-throughput single-cell RNA sequencing (scRNA-seq) to characterize the most heterogeneous class of retinal interneurons, amacrine cells, identifying 63 distinct types. The atlas includes types identified previously as well as many novel types. We provide evidence for use of multiple neurotransmitters and neuropeptides and identify transcription factors expressed by groups of closely related types. Combining these results with those obtained previously, we proposed that the mouse retina contains 130 neuronal types, and is therefore comparable in complexity to other regions of the brain.

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Multiple cell types form the VIP amacrine cell population

Cited by 24 publications

References 148 publications

Intersectional Strategies for Targeting Amacrine and Ganglion Cell Types in the Mouse Retina

Intersectional Strategies for Targeting Amacrine and Ganglion Cell Types in the Mouse Retina

GABA release selectively regulates synapse development at distinct inputs on direction-selective retinal ganglion cells

Molecular identification of sixty-three amacrine cell types completes a mouse retinal cell atlas

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