Kostadinov, DimitarSanes, Joshua2015-09-012015Kostadinov, Dimitar, and Joshua R Sanes. 2015. “Protocadherin-dependent dendritic self-avoidance regulates neural connectivity and circuit function.” eLife 4 (1): e08964. doi:10.7554/eLife.08964. http://dx.doi.org/10.7554/eLife.08964.2050-084Xhttp://nrs.harvard.edu/urn-3:HUL.InstRepos:21460690Dendritic and axonal arbors of many neuronal types exhibit self-avoidance, in which branches repel each other. In some cases, these neurites interact with those of neighboring neurons, a phenomenon called self/non-self discrimination. The functional roles of these processes remain unknown. In this study, we used retinal starburst amacrine cells (SACs), critical components of a direction-selective circuit, to address this issue. In SACs, both processes are mediated by the gamma-protocadherins (Pcdhgs), a family of 22 recognition molecules. We manipulated Pcdhg expression in SACs and recorded from them and their targets, direction-selective ganglion cells (DSGCs). SACs form autapses when self-avoidance is disrupted and fail to form connections with other SACs when self/non-self discrimination is perturbed. Pcdhgs are also required to prune connections between closely spaced SACs. These alterations degrade the direction selectivity of DSGCs. Thus, self-avoidance, self/non-self discrimination, and synapse elimination are essential for proper function of a circuit that computes directional motion. DOI: http://dx.doi.org/10.7554/eLife.08964.001en-USretinastarburst amacrine cellsynapse eliminationself-recognitiondirection selectivitymouseJournal Article2015-09-0110.7554/eLife.08964