Blue cone bipolar cells (blue CBCs) are highly conserved among mammals. Their long, meager dendrites reach for a handful of blue cones and their large axon terminals descend to the bottom of the inner plexiform layer (IPL). In the primate retina, blue CBCs relay the blue-On signals to small bi-stratified ganglion cells, which also receive red/green-Off input and give a blue-On, yellow-Off response. In the mouse retina, a similar type of blue CBC has been identified, which receives inputs from cones that only express blue (S-) opsin. This observed phenomena leads to the questions: how does a blue CBC make such an accurate synaptic connection and do presynaptic cone terminals play an instructive role in the targeting of blue CBCs? In the mouse retina, there is a dorsoventral patterning of M- and S-opsin. M-opsin expression peaks in the dorsal retina and tapers off towards the ventral retina, whereas S-opsin has the opposite pattern. A large proportion of cones in the middle ground express both opsins. The pattern of opsin expression is controlled in early development via thyroid hormone acting at the thyroid hormone receptor 2 (TR2) expressed in cones. In Thrb2-/- (TR2 deficient) mice, M-opsin expression is abolished and all cones become blue cones. We propose to study how the blue CBCs develop facing such a dramatic change in their afferent input in Thrb2-/- mice. We plan to cross the Thrb2-/- mouse line with a transgenic mouse line (Clomeleon-GFP;Clm) in which the blue CBCs (among some other cells) are GFP-labeled and easily recognizable. Currently, we are collecting data from wildtype animals and breeding two mouse lines to obtain heterozygous, and homozygous mice. by analyzing the morphology of blue CBCs in these mice, we will be able to shed light on mechanisms involved in dendritic development and synaptic targeting of blue CBCs.
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