Kostadinov and Sanes 1 PROTOCADHERIN - DEPENDENT DENDRITIC SELF - AVOIDANCE REGULATES NEURAL 1 CONNECTIVITY AND CIRCUIT FUNCTION

17 Dendritic and axonal arbors of many neuronal types exhibit self-avoidance, in which branches 18 repel each other. In some cases, these neurites interact with those of neighboring neurons, a 19 phenomenon called self/non-self discrimination. The functional roles of these processes remain 20 unknown. Here, we used retinal starburst amacrine cells (SACs), critical components of a 21 direction-selective circuit, to address this issue. In SACs, both processes are mediated by the 22 gamma-protocadherins (Pcdhgs), a family of 22 recognition molecules. We manipulated Pcdhg 23 expression in SACs and recorded from them and their targets, direction-selective ganglion cells 24 (DSGCs). SACs form autapses when self-avoidance is disrupted and fail to form connections 25 with other SACs when self/non-self discrimination is perturbed. Pcdhgs are also required to 26 prune connections between closely spaced SACs. These alterations degrade the direction 27 selectivity of DSGCs. Thus, self-avoidance, self/non-self discrimination, and synapse elimination 28 are essential for proper function of a circuit that computes directional motion. 29