Roundabout receptor 2 maintains inhibitory control of the adult midbrain

Although no two people are alike, we all share the same basic brain structure. This similarity arises because the same developmental program takes place in every human embryo. Specific genes are activated in a designated sequence to generate the structure of a typical human brain. But what happens to these genes when development is complete – do they remain active in the adult brain? A gene known as Robo2 encodes a protein that helps neurons find their way through the developing brain. Many of these neurons will ultimately form part of the brain’s reward system. This is a network of brain regions that communicate with one another using a chemical called dopamine. The reward system contributes to motivation, learning and memory, and also underlies drug addiction. In certain mental illnesses such as Parkinson’s disease and schizophrenia, the dopamine-producing neurons in the reward system work incorrectly or die. To find out whether Robo2 is active in the mature nervous system, Gore et al. used genetic techniques to selectively remove the gene from the reward system of adult mice. Doing so reduced the ability of the dopamine neurons within the reward system to inhibit one another, which in turn increased their activity. This changed the behavior of the mice, making them hyperactive and less able to learn and remember. Cocaine makes normal mice more active; however, mice that lacked the Robo2 gene became less active when given cocaine. Overall, the work of Gore et al. suggests that developmental axon guidance genes remain important in the adult brain. Studying developmental genes such as Robo2 may therefore open up new treatment possibilities for a number of mental illnesses and brain disorders.