July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Nicotinic Acetylcholine Receptors in Bipolar Cells Contribute to Motion Detection in Ganglion Cells and Optomotor Response in the Mouse Retina
Author Affiliations & Notes
  • Leo Hall
    Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Grosse Pointe Park, Michigan, United States
  • Chase B Hellmer
    Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Grosse Pointe Park, Michigan, United States
  • Christina Koehler
    Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Grosse Pointe Park, Michigan, United States
  • Tomomi Ichinose
    Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Grosse Pointe Park, Michigan, United States
  • Footnotes
    Commercial Relationships   Leo Hall, None; Chase Hellmer, None; Christina Koehler, None; Tomomi Ichinose, None
  • Footnotes
    Support  NIH EY028915, Alpha Omega Alpha (AOA) Carolyn L. Kuckein Student Research Fellowship
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 5278. doi:
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    • Get Citation

      Leo Hall, Chase B Hellmer, Christina Koehler, Tomomi Ichinose; Nicotinic Acetylcholine Receptors in Bipolar Cells Contribute to Motion Detection in Ganglion Cells and Optomotor Response in the Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5278.

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

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Abstract

Purpose : Motion detection is performed by a unique retinal neural network comprised primarily of starburst amacrine cells (SACs) and direction selective ganglion cells (DSGCs). Underlying direction selective mechanisms, however, remain unclear. We recently found that some bipolar cells (BCs), including type 7 BCs, express a7 nicotinic acetylcholine receptors (a7 nAChRs). As SACs are the only retinal neurons that release acetylcholine, BCs expressing a7 nAChRs likely play a role in motion detection. We generated mice from which a7 nAChRs are eliminated in type 7 BCs, and tested these mice by recording direction selectivity in ON-OFF DSGCs, and by assessing their optomotor responses (OMR).

Methods : Conditional a7 nAChR knockout mice were generated by crossing Chrna7-loxP and Gus-GFP mice, followed by intraocular injection with AAV (adeno-associated virus) vectors containing Cre-DOG (Cre-dependent-on-GFP) constructs. a7 nAChR expression was assessed by immunostaining with Alexa-conjugated α-bungarotoxin. Patch clamp recordings were conducted from ON-OFF DSGCs in C57BL/6J and transgenic mice. OMRs were measured to assess contrast sensitivity. Stimulus velocity was also varied and contrast sensitivities measured.

Results :
Two months after AAV-Cre-DOG injection, a7 nAChRs were eliminated from type 7 BCs. Patch clamp recordings of ON-OFF DSGCs from a7 nAChR knockout mice (n=4) demonstrated a significantly decreased direction selective index (DSI) (p<0.05) as compared to ON-OFF DSGCs taken from C57 control mice (n=4). Contrast sensitivities detected by the OMR measurement were also significantly reduced (p<0.05) in a7 nAChR knockout mice (n=10) compared to control mice (n=10). Similar decreases in contrast sensitivity were seen with transgenic (n=8) vs. control mice (n=12) when varying the stimulus velocity.

Conclusions :
With respect to the motion detection circuit, bipolar cell contributions have been dismissed. We demonstrated for the first time that a7 nAChRs in a subset of bipolar cells are critical for direction selectivity in DSGCs, as evidenced by cellular recordings and in vivo behavioral studies.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

 

Diagram shows responses of ON-OFF DSGCs evoked by moving bar stimuli. Transgenic line demonstrates marked decrease in direction selectivity as compared to wild-type line.

Diagram shows responses of ON-OFF DSGCs evoked by moving bar stimuli. Transgenic line demonstrates marked decrease in direction selectivity as compared to wild-type line.

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