From happiness to pain: Understanding serotonin's function

In a study published today (August 22nd), in the scientific journal PLoS One, researchers at the Champalimaud Neuroscience Programme establish the effect of serotonin on sensitivity to pain using a combination of advanced genetic and optical techniques.

"Serotonin is a small molecule known to be implicated in a wide range of brain functions, from the control of sleep and appetite, to the regulation of complex emotional behaviours, This neurotransmitter is also popularly thought to contribute to feelings of well being and happiness, as some anti-depression medications work through increasing serotonin in the brain." – says Zachary Mainen, CNP director and principal investigator of the Systems Neuroscience Lab.

Serotonin's great importance led researchers to seek ways of understanding its function, but studying it has been a long-standing challenge.

"Most of the cells that produce serotonin are located in a defined cell group called the Dorsal Raphe Nucleus (DRN)" – explains Zachary Mainen. "This cell group is small and located deep in the brain, which makes targeting it difficult. In addition, other cells that produce and release different molecules are also present in the DRN, which means that general stimulation of the area may result in the release of other molecules besides serotonin."

"To overcome the limitations of previous studies and explore the specific function of serotonin, we used a combination of light and genetics, an approach called optogenetics" – says Guillaume Dugué, a former postdoctoral researcher in the lab of Zachary Mainen. Using genetic techniques, the researchers expressed a light-sensitive protein specifically in the serotonin-producing cells of mice, so that when the researchers shone light on these cells, the cells released serotonin.

"The effect of the serotonin was clear" – says Guillaume Dugué. "Mice that we stimulated to release serotonin showed a significant decrease in sensitivity to pain, when compared with mice in the control group."

"We devoted substantial efforts to optimising light activation of serotonin-producing cells. Overall these results provide a new level of evidence on the importance of serotonin in gating the influence of sensory inputs to behavioural outputs, a key physiological role that will help define large-scale theories of serotonin function. Moreover, it has possible implications for better understanding chronic pain treatment." – concludes Zachary Mainen.

Zach Mainen studied psychology and philosophy at Yale University and received his PhD in Neuroscience from the University of California, San Diego in 1995. From 1995-2007 he worked at Cold Spring Harbor Laboratory, New York, first as a postdoctoral fellow and then as Assistant and Associate Professor. In 2007 Mainen moved to Lisbon, Portugal to help establish the Champalimaud Neuroscience Programme (CNP). He is currently a Senior Investigator and Director of the Programme.

In 2009 Mainen received the Senior Investigator award from the European Research Council (ERC), and in 2010 he was elected a member of the European Molecular Biology Organization (EMBO) in recognition for his work in the life sciences. Mainen's research interests concern how brains use sensory information to guide decisions and to acquire and evaluate knowledge. His laboratory's research combines quantitative descriptions of behavior with physiological analysis of neural systems and circuits and theoretical models of brain function.

The CNP is an international programme which strives to unravel the neural basis of behaviour. The concept of the programme takes into account the fact that basic neuroscience research can have a significant impact on the understanding of brain function, which in turn may contribute to the understanding and possible treatment of neurological and psychiatric illnesses.