Study
provides insight into the role of serotonin in neural plasticity
June
26, 2018
Sainsbury
Wellcome Centre
A
new computational-model reveals that serotonin, one of the most widespread
chemicals in the brain, can speed up learning.
A
new computational-model designed by researchers at UCL based on data from the
Champalimaud Centre for the Unknown reveals that serotonin, one of the most
widespread chemicals in the brain, can speed up learning.
Serotonin
is thought to mediate communications between neural cells and play an essential
role in functional, and dysfunctional, cognition. For a long time, serotonin
has been recognized as a major target of antidepressants
(selective-serotonin-reuptake-inhibitor (SSRIs) that are used to treat various
psychiatric conditions, such as depression, obsessive-compulsive-disorder and
forms of anxiety. However, serotonin in humans, and other animals, is
associated with a bewildering variety of aspects of cognition and
decision-making, including punishment, reward and patience.
The
new results, published in Nature Communications today, provide
additional illumination. In the article, Kiyohito Iigaya and Peter Dayan at
Gatsby Computational Neuroscience Unit and the Max Planck UCL Centre for
Computational Psychiatry and Ageing Research at UCL, analysed data collected by
their collaborators, Madalena Fonseca and Masayoshi Murakami, led by Zachary
Mainen at the Champalimaud Centre for Unknown in Portugal.
In
the experiments, mice were trained to choose one of the two targets to receive
water rewards. Mice continually had to learn which of the targets was more
rewarding, as the reward rates changed without warning. Crucially, sometimes
serotonin release in the brain was temporarily boosted in mice with genetically
modified serotonin neurons by a technique called optogenetics, allowing the
effects of serotonin on learning to be assessed.
Iigaya
built a computational account of mice behaviour based on reinforcement learning
principles, which are widely used in machine-learning and AI. Iigaya found that
the learning rate, i.e. how fast the modelled mice learn, was modulated by
serotonin stimulation. He compared trials with and without stimulation of
serotonin neurons, and observed that the learning rate was significantly faster
when stimulation was delivered, meaning that boosting serotonin sped up
learning in mice.
The
authors also found that when mice made decisions in very quick succession, they
followed a simple strategy called 'win-stay lose-switch', in which they
repeated a choice if it had just been rewarded, and switched to the other
choice if it had not been rewarded. Serotonin stimulation did not affect these
fast choices. However, on subset of trials, when animals acted slowly and took
a long time in-between trials, their decisions did not follow the simple
win-stay lose-switch rule. Instead, the mice made decisions based on a longer
history of rewards, which was well-characterized by a reinforcement learning
account. Serotonin stimulation only affected this slow learning system.
Importantly,
the authors found that this slow system tracked reward outcomes every trial,
even when the choices were made by the fast, win-stay lose-switch, system.
Thus, the effects of the serotonin stimulation to boost the slow system became
apparent only occasionally, when the animals spent a long time before making
decisions. The authors believe that the way that multiple decision-systems mask
each other might explain why scientists have had difficulty in constructing a
comprehensive theory as to how serotonin affects learning and decision-making.
The
authors conclude: "Our results suggest that serotonin boosts [brain]
plasticity by influencing the rate of learning. This resonates, for instance,
with the fact that treatment with an SSRI can be more effective when combined
with so-called cognitive behavioral therapy, which encourages the breaking of
habits in patients."
Substantial
clinical research shows that SSRI treatment is often most effective if combined
with cognitive-behavioural-therapy (CBT). The goal of CBT is to change
maladaptive thinking and behaviour actively, through sessions that are designed
for patients to (re)learn their way to think and behave. However, scientists
have had limited understanding of how and why SSRI and CBT work together for
treatments. The new findings point to a possible functional link between the
two, with serotonin boosting the learning inherent to CBT, providing clues as
to one of the roles that this neuromodulator plays in the treatment of
psychiatric disorders.
Story
Source:
Materials
provided by Sainsbury
Wellcome Centre. Note: Content may be edited for style and length.
Journal
Reference:
Kiyohito
Iigaya, Madalena S. Fonseca, Masayoshi Murakami, Zachary F. Mainen, Peter
Dayan. An effect of serotonergic stimulation on learning rates for rewards
apparent after long intertrial intervals. Nature Communications, 2018; 9
(1) DOI: 10.1038/s41467-018-04840-2
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