Synapse formation is arrested in retinal photoreceptors of the zebrafish nrc mutant

We describe the effects of a recessive mutation on visual behavior, the ele ctroretinogram (ERG), and photoreceptor structure in zebrafish, At 6 d post -fertilization (dpf), no optokinetic reflex could be elicited in no optokin etic response c (nrc) mutant animals under any test condition, The animals exhibited ERG responses at 5-7 dpf that were markedly abnormal and could be categorized into two groups. The first showed an initial negative a-wave f ollowed by a delayed positive b-wave of small amplitude. Often a second ERG -like response was recorded after the initial b-wave. The second group show ed only a large negative a-wave; an initial b-wave was not evident. In most recordings additional oscillatory waves varying in number, amplitude, and time course were observed, Multiple responses at the cessation of long-dura tion flashes were also observed. Light and electron microscopy revealed tha t the cone photoreceptor pedicles of nrc fish were highly abnormal. Althoug h the appropriate number of synaptic ribbons formed in these terminals, the y "floated" in the terminal, unassociated with postsynaptic processes or ar ciform densities. The few processes invaginating the nrc pedicles resembled those of horizontal cells. Invaginating bipolar cell processes were rare, but basal contacts were observed on pedicle surfaces. The severity of the m utation did not change between 6 and 8 dpf, showing that there is neither a delay in development nor a degeneration of the terminals; rather, nrc pedi cle development appears arrested. Bipolar cell terminals in the inner plexi form layer made normal ribbon synapses; thus, the mutation appears to affec t only the outer retina.