title: Protocadherin-dependent dendritic self-avoidance regulates neural connectivity and circuit function.
abstract: Dendritic 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.
authors.affiliation: Center for Brain Science, Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States.
authors.forename: Dimitar
authors.initials: D
authors.lastname: Kostadinov
authors.affiliation: Center for Brain Science, Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States.
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Sanes
mesh_terms: D025042:Amacrine Cells / Q000187:drug effects* / Q000502:physiology*; D000818:Animals; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000378:metabolism*; D003712:Dendrites / Q000187:drug effects* / Q000502:physiology*; D008810:Mice, Inbred C57BL
chemical_list: D000070585:Cadherin Related Proteins; D015820:Cadherins; C464785:Gamma-protocadherins
keywords: developmental biology; direction selectivity; mouse; neuroscience; retina; self-recognition; starburst amacrine cell; stem cells; synapse elimination