June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Genetic dissection of a new amacrine cell type shaping object motion sensitivity in the mouse retina
Author Affiliations & Notes
  • Yongling Zhu
    Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
    Neuroscience, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Steven H DeVries
    Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
    Neuroscience, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Andrew Jo
    Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
    Neuroscience, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Sercan Deniz
    Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
    Neuroscience, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Suraj Cherian
    Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
    Neuroscience, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Jian Xu
    Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
    Neuroscience, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Footnotes
    Commercial Relationships   Yongling Zhu None; Steven DeVries None; Andrew Jo None; Sercan Deniz None; Suraj Cherian None; Jian Xu None
  • Footnotes
    Support  NIH grants R01 EY030169, R01 EY018204, R01 EY012141, F31 EY031985 , Whitehall Foundation Grant, and Research to Prevent Blindness.
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 4559 – F0421. doi:
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    • Get Citation

      Yongling Zhu, Steven H DeVries, Andrew Jo, Sercan Deniz, Suraj Cherian, Jian Xu; Genetic dissection of a new amacrine cell type shaping object motion sensitivity in the mouse retina. Invest. Ophthalmol. Vis. Sci. 2022;63(7):4559 – F0421.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Amacrine cells (ACs) are the most abundant inhibitory interneurons in the retina yet remain the least understood retinal cell class. The great diversity of ACs has been a major obstacle to access individual cell types for systematic studies. The development of genetic tools that allow for cell type-specific targeting and manipulation would be an important step towards the characterization of AC types. In this study, we aim to use new mouse intersectional genetic tools combined with functional imaging and electrophysiology recording to morphologically and functionally dissect AC circuits.

Methods : We created intersectional strategies by using a combination of Cre and tTA expression to discover new AC types and to target these cells with increased specificity. After that, we focused on a new AC type for functional analysis. We characterized its light response properties by imaging Ca2+ responses at the sites of neurotransmitter release, and then identify its post-synaptic RGCs with intersectional ChR2 activation. Finally, we developed a chemogenetic mouse line to inactivate the AC and examine its functional roles in different circuits.

Results : With Slc32a1-iCreER/ CaMK2a-tTA intersectional strategy combined with temporally controlled Cre induction, we discovered a narrow-field AC subtype (named CK2-AC1) in the mouse retina and achieved single AC type targeting. Two-photon Ca2+ imaging revealed that CK2-AC1 received synaptic inputs from OFF bipolar cells and responded strongly to local motion but not to global motion. Optogenetic stimulation showed that CK2-AC1 provided glycinergic inputs to several RGC types stratified in the middle of the IPL, such as HD1-RGC and HD2-RGC. Chemogentic inactivation experiments further demonstrated that CK2-AC1 provided suppression to several RGC types during local stimulation and shape the object motion sensitivity (OMS) of these RGCs.

Conclusions : This study introduced a workflow based on Cre/tTA intersectional strategies for systematically analyzing AC types and examining their circuit roles in visual processing. With this workflow, we discovered a new AC type and revealed its functional roles in the OMS circuits. We propose that CK2-AC1, together with other ACs in the OMS circuits, controls the objective motion sensitive signals RGC send to the brain.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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