Behavioral tests based on CNS-controlled visual responses have been used in functional analyses of zebrafish visual system development and visual performance. While the behavioral startle and phototactic response assays test simply the light response, OKR, OMR, and escape response assays examine directly visual acuity and visual sensitivity (Kimmel et al., 1974; Clark, 1981; Brockerhoff et al., 1995; Easter and Nicola, 1996; Li and Dowling, 1997; Neuhauss et al., 1999). The OKR, OMR, and escape response assays are sensitive and robust, allowing for the screening of visual system mutations without the preconception of gross eye morphologic abnormalities. It is expected that, in the near future, other behavioral or behavioral-psychological assays will be developed to study high-level visual functions and to isolate mutations that cause subtle defects in the visual pathway, for example, mutations that affect spatial and frequency sensitivity or contrast sensitivity (Baier, 2000; Orger et al., 2000).
To date, mutations in many genes that affect zebrafish visual system development and function have been identified. However, most of these mutations have only been preliminarily studied (Karlstrom et al., 1996; Malicki et al., 1996; Trowe et al., 1996; Link et al., 2000; Malicki and Driever, 1999). In the future, these mutations will be further characterized. By examining cell morphology or by using cell-specific antibodies, for example, one would be able to determine the cell types that are affected by the mutated genes (Kimmel et al., 1995; Westerfield, 1995; Talbot et al., 1995; Connaughton and Dowling, 1998; Connaughton et al., 1999; Vihtelic et al., 1999; Kennedy et al., 2001). In addition, physiological assays that permit the direct analyses of retinal neuronal properties should be further developed. To date, several in vivo electrophysiological assays, such as the electroretinographic and ganglion cell spike recordings, have been used in the analysis of zebrafish outer and inner retinal functions (Branchek, 1984; Brockerhoff et al., 1995; Li and Dowling, 1997, 2000a; Hughes et al., 1998; Saszik et al., 1999). However, intracallular or tectum recording techniques have not been explored in the mutants (Sajovic and Levinthal, 1982a,b, 1983; McMahon, 1994; Fan and Yazulla, 1997; Connaughton and Nelson, 2000). These assays may very likely provide tools that allow one to narrow down the defects to a cellular level in the mutant retinas. The characterization of zebrafish visual system mutations will provide insights into the molecular genetics of vertebrate vision.