Distinct optokinetic reflex phenotypes in Frmd7 and Chrnb2 mutant mice

Abstract Highlights Binocular rotational stimulation enhances OKR in wild-type mice along both axes. Chrnb2tm mice show spontaneous horizontal eye oscillations regardless of input. Frmd7tm mice lack binocular enhancement of vertical OKR. The optokinetic reflex (OKR) stabilizes retinal images during global motion and depends on retinal direction-selective (DS) circuits. Although multiple mutant mouse strains exhibit impaired DS circuits via distinct mechanisms, differences in OKR phenotypes remain unexplained. Here, we developed a behavioral system to quantify mouse eye movements under controlled rotational and translational visual stimuli. Using this platform, we examined OKR in wild-type (WT) mice and two DS circuit mutants: Frmd7tm mice, which lack horizontal DS tuning and horizontal OKR, and Chrnb2tm mice, which have disrupted β2-nAChR-dependent cholinergic spontaneous activity during development. Consistent with previous research, both mutants lacked horizontal OKR across conditions, while vertical OKR was preserved. We found that Chrnb2tm mice exhibited spontaneous horizontal eye oscillations regardless of visual input. This phenotype was absent in Frmd7tm mice, suggesting that defective retinal waves in Chrnb2tm mice may induce circuit-level instability distinct from the loss of horizontal DS tuning alone. In addition, WT mice showed enhanced vertical OKR under binocular rotational stimulation, which was absent in Frmd7tm mice. Together, these findings provide a functional comparison of Frmd7tm and Chrnb2tm mice and establish a quantitative framework for dissecting how specific genetic perturbations alter the retinal computations underlying horizontal and vertical OKR. Competing Interest Statement The authors have declared no competing interest.