In addition to the cellular rearrangements that establish synaptic specificity check details among converging excitatory inputs, the signals which instruct these rearrangements are poorly understood. We previously found that glutamate release from BCs regulates the total number of synapses formed on retinal ganglion cell (RGC) dendrites (Kerschensteiner et al., 2009). Here, we test whether this

regulation depends on the afferent cell type and thus shapes the development of specific connectivity patterns. Twelve types of BCs relay different components of photoreceptor signals from the outer to the inner plexiform layer (IPL) of the retina (Wässle et al., 2009). As in many other parts of the nervous system, connections in the IPL are organized into laminar circuits (Sanes and Zipursky, 2010 and Wässle, 2004). Accordingly, axons of different BC types target distinct depths of the IPL where they innervate RGCs that stratify their dendrites at the same depth. Developing BCs elaborate axonal arbors from neuroepithelial-like precursor processes, extending side branches throughout the IPL of which they selectively stabilize those located at the correct depth (Morgan et al., 2006). BC axons attain

their final laminar position before the retina processes visual information and continue to form and eliminate synapses with RGC dendrites at high rates for more than a week after laminar targeting is complete (Kerschensteiner et al., 2009 and Morgan et al., 2008). How retinal circuits are rewired by this synaptic remodeling after laminar targeting remains Resminostat unknown. Combining different Epigenetics Compound Library chemical structure genetic labeling techniques and imaging

approaches we examined the development of synapses from three types of BCs with a single type of RGC in vivo. We find that the different BC axons initially connect equally to the shared RGC dendrite. Synaptic patterns of the different BC types diverge only after laminar targeting is complete. This is achieved by selective changes in the conversion of axo-dendritic appositions to synapses. Neurotransmission regulates this process in a cell type-dependent manner and thus shapes synaptic specificity among converging excitatory axons. To observe directly how different afferents establish specific patterns of connections with a common target, we fluorescently labeled pairs of neurons and their connections in the intact developing retina. Pairs consisted of one of three BC types and a single RGC type. Of the twelve BC types found in mice (Wässle et al., 2009) eleven receive input from cone photoreceptors and one from rods. Five cone BC types (B1, B2, B3a, B3b, B4) express ionotropic glutamate receptors on their dendrites and depolarize in response to light decrements (OFF BCs) (Haverkamp et al., 2001a and Haverkamp et al., 2001b).