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.
Nerve cells (or neurons) connect to one another to form circuits that control the animal's behavior. Typically, each neuron receives signals from other cells via branch-like structures called dendrites. Each specific type of neuron has a characteristic pattern of branched dendrites, which is different from the pattern of other types of neuron. Therefore, it is reasonable to imagine that the shape of these branches can influence how the neuron works; however, this idea has rarely been tested experimentally.
Different processes are known to act together to control the pattern of the branched dendrites. For example, dendrites in some neurons avoid other dendrites from the same neuron. This phenomenon is referred to as ‘self-avoidance’. In some of these cases, the same dendrites freely interact with the dendrites of neighboring neurons of the same type; this is called ‘self/non-self discrimination’. It is not clear, however, how these two processes influence the activity of neural circuits.
Both self-avoidance and self/non-self discrimination rely on the expression of genes that encode so-called recognition molecules. Kostadinov and Sanes have now altered the expression of these genes in mice to see the effect that disrupting these two phenomena has on a set of neurons called ‘starburst amacrine cells’ that are found at the back the eye. The dendrites of starburst amacrine cells generate signals when objects move across the animal's field of vision. These dendrites then signal to other starburst amacrine cells and to so-called ‘direction-selective ganglion cells’, which in turn send this information to the brain for further processing. The experiments revealed that these disruptions affected the connections between the dendrites. Starburst amacrine cells that lacked self-avoidance mistakenly formed connections with themselves—as if they mistook their own dendrites for those of other starburst cells. In contrast, neurons that lacked self/non-self discrimination made the opposite mistake, and rarely formed connections with each other—as if they mistook the dendrites of other starbursts for their own. Disruptions to either phenomenon interfered with the activity of the direction-selective ganglion cells.
Following on from the work of Kostadinov and Sanes, the next challenges include uncovering how the recognition molecules help with self-avoidance and self/non-self discrimination. It will also be important to examine whether the conclusions based on one type of neurons can be generalized to others that also exhibit these two phenomena.