In a study published 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.
For more information
Activation of Dorsal Raphe Serotonergic Neurons
Promotes Waiting but Is Not Reinforcing