Protocadherin-dependent dendritic self-avoidance regulates neural connectivity and circuit function

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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. Here, 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.

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Dimitar Kostadinov

Center for Brain Science, Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States

Competing interests
The authors declare that no competing interests exist.
Joshua R Sanes

Center for Brain Science, Department of Molecular and Cellular Biology, Harvard University, Cambridge, United States

For correspondence
sanesj@mcb.harvard.edu

Competing interests
The authors declare that no competing interests exist.

Ethics

Animal experimentation: Animals were used in accordance with NIH guidelines and protocols approved by Institutional Animal Use and Care Committee at Harvard University (IACUC protocol #24-10).Animals were euthanized by intraperitoneal injection of pentobarbital or euthasol.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.