What do we know:
Serotonin—a 'happiness' molecule in the brain—is important for making social decisions. The ventromedial prefrontal cortex is important for deciding what emotion we attach to things or people.
What don’t we know: The specific way the brain is wired to control serotonin when we are deciding to approach or avoid a stranger.
What this study shows: We can control whether a mouse approaches or avoids a new social partner by changing the activity of prefrontal cortical neurons that communicate with cells that inhibit serotonin neurons.
What we can do in the future because of this study: We could find out if dysfunction in this brain wiring contributes to social symptoms of mood disorders and whether changing activity of this circuit can improve behavior. Future findings could also determine how changing the activity of this brain pathway affects serotonin actions in other brain regions, both long- and short-term.
Why you should care: Current antidepressants, which broadly target serotonin in the brain, do not work well for many people. Instead of affecting all serotonin in the brain, new treatments that target specific parts of the brain (like the regions described here) may be more effective at treating patients with mood disorders.
When we meet strangers, we make social decisions, including whether we want to approach or avoid them. These are based on social judgments made immediately and often unconsciously. People that are diagnosed with mood disorders, such as depression and anxiety disorders, often excessively avoid other people. Therefore, understanding how these social decisions are made can help us design new therapies to treat disorders involving skewed social decisions. Researchers have shown that altering levels of serotonin—a molecule in the brain thought to contribute to 'happiness'—can influence these decisions; however, scientists do not know which parts of the brain communicate to control this. In our study, we investigated how communication between a brain area important for processing social information (the prefrontal cortex) and a brain area that provides serotonin to the rest of the brain (the dorsal raphe) can affect social approach or avoidance decisions in mice. With a technique called optogenetics, which uses light from a laser to either increase or decrease communication between the prefrontal cortex and the dorsal raphe, we were able to change the social decisions made by mice. Understanding how brain wiring affects social behavior will improve our comprehension of mood disorders, such as depression, which may allow development of better therapies to treat those people affected.
Though it has long been known that serotonin can alter social perception, the underlying neural circuits that control serotonergic output during social interaction are complex. Previous mapping studies have shown that the ventromedial prefrontal cortex (vmPFC), an area of the brain believed to be important for encoding emotional value, sends excitatory projections to the serotonergic dorsal raphe nucleus (DRN). In this study, we first show that these vmPFC afferents actually synapse directly on GABA neurons in the DRN that then locally inhibit serotonin neurons. We then used optogenetics to manipulate this specific and direct pathway from the vmPFC to the DRN during social defeat, a paradigm that exposes mice to physical and sensory contact with a larger, more aggressive strain of mice and induces a long lasting form of social avoidance. We found that blocking vmPFC inputs to the DRN, thus disinhibiting serotonin neurons, prevented the social avoidance typically observed after defeat. Conversely, when we optogenetically activated the vmPFC terminals, these mice displayed strong social avoidance and a considerable delay in their decision to approach a social partner. Dissecting the role of the vmPFC-DRN in social decisions has implications for the social symptoms observed in mood disorders as well as the development of novel therapeutic treatments for these behaviors.