In a study published today (January 15th 2015) in the journal Current Biology, a team of scientists, led by Zachary Mainen at the Champalimaud Centre for the Unknown (CCU), found a causal link between the activation of serotonin neurons and the amount of time mice are willing to wait, and rejected a possible link between increased serotonin neuron activation and reward.

Serotonin is a neuromodulatory chemical that is targeted by antidepressant drugs, such as Prozac, which are widely used to treat depression and other disorders such as chronic pain. Serotonin is normally released by a small set of cells in an area of the brain called the raphe nuclei. However, what naturally causes these neurons to become active and release serotonin and how this affects brain function are still poorly understood.

To investigate the role of serotonin in patience, the researchers used a task in which mice have to wait for a reward that arrives at random times. During some of the trials, they stimulated serotonin neurons using a technique called optogenetics. "We made serotonin neurons sensitive to light, so when we illuminated them, they were activated and released serotonin in the brain", said Madalena Fonseca, team member at the CCU.

The scientists observed that when they activated serotonin neurons, mice became more patient. Explained Masayoshi Murakami, also part of the CCU team, "we tested how different levels of activation influence waiting and saw that stronger activation resulted in longer waiting durations - the more serotonin neurons were activated, the longer the mice would wait."

To test whether increased waiting was a side effect of another serotonin function, the scientists performed experiments to test if stimulation of serotonin neurons could act as a reward. "If the sensation of serotonin was pleasant or rewarding for the mice, this could have explained why they waited longer", said Fonseca. To do this, they tested whether mice preferred to perform actions associated with serotonin stimulation. The results of these experiments were negative, ruling out that increased patience was a consequence of reward.

This study has implications for understanding the involvement of serotonin in depression and other diseases. "Because antidepressants are thought to increase serotonin, people assume that more serotonin neuron firing would feel good. Our results show that the story is not so simple. That serotonin affects patience gives us an important clue that we hope will help us crack the serotonin mystery", said Zachary Mainen. The Champalimaud team is continuing to investigate other aspects of serotonin function in work funded by the European Research Council.

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About Zachary Mainen, Principal Investigator and Director of the Champalimaud Neuroscience Programme

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.

About the Champalimaud Neuroscience Programme (CNP)

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.

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