Spectral inference reveals principal cone-integration rules of the zebrafish inner retina

Retinal bipolar cells integrate cone signals at dendritic and axonal sites. The axonal route, involving amacrine cells, remains largely uncharted. However, because cone types differ in their spectral sensitivities, insights into bipolar cells' cone integration might be gained based on their spectral tunings. We therefore recorded in vivo responses of bipolar cell presynaptic terminals in larval zebrafish to widefield but spectrally resolved flashes of light and mapped the results onto spectral responses of the four cones. This "spectral circuit mapping" allowed explaining ~95% of the spectral and temporal variance of bipolar cell responses in a simple linear model, thereby revealing several notable integration rules of the inner retina. Bipolar cells were dominated by red-cone inputs, often alongside equal sign inputs from blue and green cones. In contrast, UV-cone inputs were uncorrelated with those of the remaining cones. This led to a new axis of spectral opponency where red-, green-, and blue-cone "Off" circuits connect to "natively-On" UV-cone circuits in the outermost fraction of the inner plexiform layer-much as how key color opponent circuits are established in mammals. Beyond this, and despite substantial temporal diversity that was not present in the cones, bipolar cell spectral tunings were surprisingly simple. They either approximately resembled both opponent and non-opponent spectral motifs already present in the cones or exhibited a stereotyped non-opponent broadband response. In this way, bipolar cells not only preserved the efficient spectral representations in the cones but also diversified them to set up a total of six dominant spectral motifs, which included three axes of spectral opponency.