Early physiological recordings suggested that there were four types of bipolar cells: ON, OFF, sustained, and transient (Kaneko, 1970; Werblin and Dowling, 1969). Modern anatomical work and subsequent physiological evidence indicate that the true number of bipolar cell types is about 12. This has been a gradual realization. Initial studies used synapse densities (Cohen and Sterling, 1990) to distinguish the types. As marker proteins of increasing specificity

were discovered, the number of putative bipolar cell types gradually increased. Recent studies seem to have brought this to its conclusion. A set of intersecting methods find more was used to classify the bipolar cells of the rabbit (MacNeil et al., 2004). The strategy was to seek a complete survey of bipolar cell types by using several methods with different sampling biases. For purposes of classification, the purely anatomical Anti-diabetic Compound Library cell line samples were complemented by a set of cells injected with Lucifer yellow after physiological recording, so that their responses to light could be used as part of the classification. The bipolar cells of the rabbit were divided into a rod bipolar cell and 12 types of cone bipolar cells. In near-perfect agreement, Wässle et al. (2009) classified

the bipolar cells of the mouse using immunostaining for recently discovered type-specific markers and transgenic strains in which one or a few types of bipolar cells express a fluorescent marker. These were supplemented by microinjection, to reveal the cells’ finest processes and their contacts. They found one type of rod Levetiracetam driven bipolar cell and 11 types that receive inputs primarily from cones (Figure 2). Because they are population stains, these methods allowed an estimate of the total number of bipolar cells of each type, which could

then be added up for comparison with the total number of bipolar cells known by independent methods to exist in the mouse (Jeon et al., 1998). The identified individual cell types correctly added up to the known total number of bipolar cells. Thus, “…the catalog of 11 cone bipolar cells and one rod bipolar cell is complete, and all major bipolar cell types of the mouse retina appear to have been discovered” (Wässle et al., 2009). This concept is simple, but it is topologically fairly subtle (Figure 3). From partial evidence, it was suspected a decade ago that each cone makes output to each of the types of bipolar cells—a critical principle for the signal processing of the retina. Wässle et al. (2009) could confirm that this occurs for each of the 11 types of bipolar cells that they identified in the mouse. The exception is a specialized “blue cone bipolar,” which selectively contacts the short wavelength sensitive cones, as is necessary if the chromatic information is not to be degraded. Symmetrically, some bipolar cells avoid the terminals—they are numerically infrequent—of blue cones. And there is some crosstalk with the rods.