TY - JOUR
T1 - A common cause for nystagmus in different congenital stationary night blindness mouse models
AU - Hölzel, Maj-Britt
AU - Kamermans, Wouter
AU - Winkelman, Beerend H. J.
AU - Howlett, Marcus H. C.
AU - de Zeeuw, Chris I.
AU - Kamermans, Maarten
N1 - Funding Information: This research was funded by EU-Horizon 2020, via the SwitchBoard grant, a grant from the friends foundation of the Netherlands Institute for neuroscience, by Uitzicht grants UT2016-13 and UT 2020-14, a generous donor via the Friends of the Netherlands Institute of Neuroscience Foundation, the Netherlands Organization for Scientific Research (NWO-ALW 824.02.001), the Dutch Organization for Medical Sciences (ZonMW 91120067), Medical Neuro-Delta (MD 01092019−31082023), INTENSE LSH-NWO (TTW/00798883), ERC-adv (GA-294775) and ERC-POC (nos. 737619 and 768914), and the NIN Vriendenfonds for Albinism as well as the Dutch NWO Gravitation Program (DBI2). The authors would like to thank Cynthia Geelen for genotyping the mice. Funding Information: This research was funded by EU‐Horizon 2020, via the SwitchBoard grant, a grant from the friends foundation of the Netherlands Institute for neuroscience, by Uitzicht grants UT2016‐13 and UT 2020‐14, a generous donor via the Friends of the Netherlands Institute of Neuroscience Foundation, the Netherlands Organization for Scientific Research (NWO‐ALW 824.02.001), the Dutch Organization for Medical Sciences (ZonMW 91120067), Medical Neuro‐Delta (MD 01092019−31082023), INTENSE LSH‐NWO (TTW/00798883), ERC‐adv (GA‐294775) and ERC‐POC (nos. 737619 and 768914), and the NIN Vriendenfonds for Albinism as well as the Dutch NWO Gravitation Program (DBI2). Publisher Copyright: © 2023 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.
PY - 2023/12/1
Y1 - 2023/12/1
N2 - Abstract: In Nyxnob mice, a model for congenital nystagmus associated with congenital stationary night blindness (CSNB), synchronous oscillating retinal ganglion cells (RGCs) lead to oscillatory eye movements, i.e. nystagmus. Given the specific expression of mGluR6 and Cav1.4 in the photoreceptor to bipolar cell synapses, as well as their clinical association with CSNB, we hypothesize that Grm6nob3 and Cav1.4-KO mutants show, like the Nyxnob mouse, oscillations in both their RGC activity and eye movements. Using multi-electrode array recordings of RGCs and measurements of the eye movements, we demonstrate that Grm6nob3 and Cav1.4-KO mice also show oscillations of their RGCs as well as a nystagmus. Interestingly, the preferred frequencies of RGC activity as well as the eye movement oscillations of the Grm6nob3, Cav1.4-KO and Nyxnob mice differ among mutants, but the neuronal activity and eye movement behaviour within a strain remain aligned in the same frequency domain. Model simulations indicate that mutations affecting the photoreceptor–bipolar cell synapse can form a common cause of the nystagmus of CSNB by driving oscillations in RGCs via AII amacrine cells. (Figure presented.). Key points: In Nyxnob mice, a model for congenital nystagmus associated with congenital stationary night blindness (CSNB), their oscillatory eye movements (i.e. nystagmus) are caused by synchronous oscillating retinal ganglion cells. Here we show that the same mechanism applies for two other CSNB mouse models – Grm6nob3 and Cav1.4-KO mice. We propose that the retinal ganglion cell oscillations originate in the AII amacrine cells. Model simulations show that by only changing the input to ON-bipolar cells, all phenotypical differences between the various genetic mouse models can be reproduced.
AB - Abstract: In Nyxnob mice, a model for congenital nystagmus associated with congenital stationary night blindness (CSNB), synchronous oscillating retinal ganglion cells (RGCs) lead to oscillatory eye movements, i.e. nystagmus. Given the specific expression of mGluR6 and Cav1.4 in the photoreceptor to bipolar cell synapses, as well as their clinical association with CSNB, we hypothesize that Grm6nob3 and Cav1.4-KO mutants show, like the Nyxnob mouse, oscillations in both their RGC activity and eye movements. Using multi-electrode array recordings of RGCs and measurements of the eye movements, we demonstrate that Grm6nob3 and Cav1.4-KO mice also show oscillations of their RGCs as well as a nystagmus. Interestingly, the preferred frequencies of RGC activity as well as the eye movement oscillations of the Grm6nob3, Cav1.4-KO and Nyxnob mice differ among mutants, but the neuronal activity and eye movement behaviour within a strain remain aligned in the same frequency domain. Model simulations indicate that mutations affecting the photoreceptor–bipolar cell synapse can form a common cause of the nystagmus of CSNB by driving oscillations in RGCs via AII amacrine cells. (Figure presented.). Key points: In Nyxnob mice, a model for congenital nystagmus associated with congenital stationary night blindness (CSNB), their oscillatory eye movements (i.e. nystagmus) are caused by synchronous oscillating retinal ganglion cells. Here we show that the same mechanism applies for two other CSNB mouse models – Grm6nob3 and Cav1.4-KO mice. We propose that the retinal ganglion cell oscillations originate in the AII amacrine cells. Model simulations show that by only changing the input to ON-bipolar cells, all phenotypical differences between the various genetic mouse models can be reproduced.
KW - A amacrine cells
KW - CSNB
KW - Ca1.4-KO
KW - Grm6
KW - Nyx
KW - congenital nystagmus
KW - eye movements
KW - retina
KW - retinal ganglion cells
UR - http://www.scopus.com/inward/record.url?scp=85174540750&partnerID=8YFLogxK
U2 - https://doi.org/10.1113/JP284965
DO - https://doi.org/10.1113/JP284965
M3 - Article
C2 - 37864560
SN - 0022-3751
VL - 601
SP - 5317
EP - 5340
JO - Journal of physiology
JF - Journal of physiology
IS - 23
ER -