LAUSR

ABSTRACT The circadian clock is an endogenous and entrainable time-keeping mechanism with a period of approximately 24 h, operated by transcription/translation feedback loops composed of circadian clock genes and their proteins. The visual system displays robust circadian changes. Relatively little, however, is known about the mechanisms underlying visual circadian rhythmicity. Zebrafish period1b (per1b), as a canonical circadian clock gene, is involved in circadian regulation. Here, we observed that zebrafish per1b mutants exhibit visual defects including reduced behavioral contrast sensitivity and significant retinal dopaminergic deficiency. Further, partially damaged dopaminergic interplexiform cells in wild-type larvae also led to reduced behavioral contrast sensitivity, while exogenous dopamine administration effectively restored the contrast sensitivity of per1b mutants. Taken together, these results suggest that retinal dopaminergic deficiency derived from loss of per1b results in visual defects in zebrafish. Abbreviations: per1b, period1b; per, period; per1, period1; per2, period2; per3, period3; ERG, electroretinogram; DA-IPCs, dopaminergic interplexiform cells; IRBP, interphotoreceptor retinoid binding protein; MS-222, methane-sulfonate; USTC, University of Science and Technology of China; OKR, optokinetic response; dpf, day postfertilization; 6-OHDA, 6-hydroxydopamine; TH, tyrosine hydroxylase; DA, dopaminergic; INL, inner nuclear; IPL, innerplexiform layers; hpf, hours postfertilization; cpd, cycle per degree; ADHD, attention deficit and hyperactivity disorder.