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Maarten Kamermans, Kathryn Fransen, Gobinda Pangeni, Marcus Howlett, Maj-Britt Holzel, Maureen A McCall, Chris Zeeuw de, Beerend Winkelman; Oscillating eye movements in nob mice are explained by oscillating ON-direction selective ganglion cells. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2232.
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Retinal motion detection is elemental to image stabilizing eye movement reflexes and is mediated by ON-direction selective ganglion cells. Here we report on eye movement control in mice without functional ON-bipolar cells (nob mice).
We studied optokinetic reflex eye movements and single cell responses retinal ganglion cells in wt and nob mice under various pharmacological conditions. Nob mice have a mutation in the X-chromosomal gene encoding for nyctalopin, causing defective signaling within the mGluR6 cascade in retinal ON-bipolar cells.
Optokinetic stimulation using sine-wave gratings showed substantial impairment of the optokinetic reflex and defective gaze holding in the nob mice. Eye movements of nob mice exhibited a prominent horizontal oscillation with an average frequency of 5 Hz. These oscillations changed with lighting conditions. Electrophysiological recordings in the retina confirmed that ON-dsGCs of nob mice are unresponsive to light stimulation, but their membrane potential showed robust sub-threshold oscillations with a frequency of 5 Hz on average. These oscillations were eliminated or significantly reduced by simultaneously blocking both the AMPA and NMDA receptors, using application of DNQX and D-AP5. Intravitreal injection of this cocktail in both eyes of nob mice abolished the 5 Hz oscillation in spontaneous eye movements, recorded while the animal was awake, which strongly suggests that synchronous oscillation of dsGCs in the retina is the direct cause of the horizontal eye movement oscillation.
The absence of functional ON-bipolar cells leads to oscillating ganglion cell responses, resulting in oscillating eye movements. This mechanism could explain the small amplitude horizontal nystagmus observed in CSNB patients (Simonsz et al., 2009).
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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