(l to r) Mackenzie Amoroso, Jeremiah Cohen, and Nao Uchida
Serotonin is one of the most widespread and mysterious neurotransmitters in the brain. It has been proposed to be involved in many aspects of behavior, including regulating mood and our responses to aversive environmental events. Furthermore, it has also been proposed that a deficiency in serotonin plays a central role in depression. One of the major challenges in testing hypotheses about serotonin’s function has been observing the activity of serotonin-releasing neurons during behavior. Historically, when we place a microelectrode into the midbrain structure that contains serotonin-releasing neurons, it was difficult to know whether the neuron under observation was releasing serotonin.
To address this problem, we used a combination of transgenic mice and optogenetics to identify serotonin neurons by their response to light stimulation. Then, we recorded the activity of these light-identified serotonin neurons as mice participated in a task in which the amount of reward or punishment available in the environment varied predictably over time. We found that 40% of serotonin neurons showed slow variations in the activity that correlated with the amount of reward in the environment. This was remarkable, as when we recorded the activity from light-identified dopamine neurons, which have long been thought to be involved in reward, they did not signal information on these slow timescales. In contrast, we found that all the dopamine neurons encoded only the immediate properties of the environment (for example, “I’m about to get a reward”), and only a fraction of the serotonin neurons signaled these immediately pending rewards. Taken together, serotonin neurons have the ability to signal reward and punishment on both slow and fast timescales. These results suggest that serotonin signals could be important for regulating our behavior on slow timescales, and may be involved in generating emotional states like mood.