Striatal fast-spiking interneurons selectively modulate circuit output and are required for habitual behavior

From biting fingernails to the daily commute, habits are sets of actions that can be completed almost without thinking and that are difficult to change or stop. Behavioral neuroscientists refer to habits as “stimulus-response” behaviors, and know that forming a new habit requires a region deep within the brain called the dorsolateral striatum. Indeed, in this region, the outgoing neurons – which make up 95% of the cells - respond differently to incoming signals in mice that have learned habits compared to non-habitual mice. However a question remained: what exactly was producing these differences? O’Hare et al. have now found, unexpectedly, that the answer resides not in the 95% of outgoing neurons, but rather in a rare type of cell known as the fast-spiking interneuron. This cell is connected to many others and it appears to act like a conductor, orchestrating the previously identified changes in the output neurons. These findings were made using mice that had been trained to press a lever for a sugar pellet reward. Habit was measured by how long mice kept pressing even if they had just been allowed to eat their fill of pellets and the test lever was no longer dispensing pellets. Habitual mice continue to press the lever in this circumstance, while other mice do not. O’Hare et al. found that inactivating the “conductor” cell made the output neurons respond in the opposite way to how they normally respond in habitual mice. Further experiments showed that fast-spiking interneurons were also more easily activated in habitual mice. To test whether this putative “conductor” cell was necessary for habitual behaviors, a technique known as chemogenetics was used to turn down its activity in habitual mice. Indeed, reducing activity in the conductor cell blocked the habitual behavior. While some habits are a helpful and economical way to get through daily life, habits are also thought to be corrupted in a number of diseases such as neurodegenerative diseases, addictions and compulsions. Identifying this specific, yet rare, cell as a critical part of maintaining habits points out a new target to consider for therapies. Further work is needed before such treatments might become available to treat habit-related disorders; though O'Hare et al. are now taking steps in this direction by trying to work out how the fast-spiking interneuron changes its own activity when a habit is formed.