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| Monterotondo, 3 June 2007 |
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| New insights into the neural basis of anxiety
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Click on the picture for a larger version
Collage of colorised images of the part of the hippocampus that is involved
in anxiety towards ambiguous stimuli in mice
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Researchers identify a neural circuit that makes mice perceive ambiguous
situations as threatening
Press
Release 3 June 2007 [PDF]
People who suffer from anxiety
tend to interpret ambiguous situations, situations that could
potentially be dangerous but not necessarily so, as threatening.
Researchers from the Mouse Biology Unit of the European
Molecular Biology Laboratory [EMBL] in Italy have now uncovered
the neural basis for such anxiety behaviour in mice. In the
current issue of Nature Neuroscience they report that a receptor
for the messenger serotonin and a neural circuit involving a brain
region called the hippocampus play crucial roles in mediating fear
responses in ambiguous situations.
A mouse that has learned that a certain cue, for example a tone, is
always followed by an electrical shock comes to associate the two
and freezes with fear whenever it hears the tone even if the shock
is not delivered. But in real life the situation is not always so clear;
a stimulus will only sometimes be followed by a threat while other
times nothing might happen. Mice show less fear towards
such ambiguous cues than to clearly threatening stimuli.
A team of researchers led by Cornelius Gross at the EMBL Mouse
Biology Unit now discovered that this response to ambiguous
stimuli requires a specific receptor molecule for serotonin, a signal
many brain cells use to communicate. Mice that lack the serotonin
receptor 1A have problems processing ambiguous stimuli
and react to them with full-fledged fear responses. The cause is
wrongly connected cells in their brains. Serotonin signalling is
very important for brain development and if the receptor 1A is
missing, defects arise in the wiring of the brain that affect the
behaviour of mice later on in life.
"In humans serotonin signalling has been implicated in disorders
including depression and anxiety and like our mice patients suffering
from these conditions also overreact to ambiguous situations,"
Gross says. "The next step was to identify the brain regions
that are responsible for such complex fear behaviour and the processing
of ambiguous cues."
Using a new technique to switch off neural activity in selective
brain cells in living mice, Gross and his colleagues discovered that
a specific part of the hippocampus is required for correct processing
of ambiguous stimuli.
"Shutting down a specific circuit in the hippocampus abolished
fear reactions only to ambiguous cues," says Theodoros Tsetsenis,
who carried out the research in Gross' lab. "The pathway must be
involved in processing and assessing the value of stimuli. It seems
to bias mice to interpret situations as threatening."
The hippocampus is mainly known as a region important for
learning and memory, but the results reveal a more general role
in evaluating information and assessing contingencies.
Neural circuits that govern fundamental behaviours like fear are
often conserved between species and patient studies suggest
a role for the hippocampus in anxiety also in humans. The new
insights gained into serotonin signalling via the receptor 1A and
the role of the hippocampus in fear behaviour in mice promise to
shed light on the neural basis of anxiety disorders and open up
new avenues for therapies.
Source Article
Tsetsenis, T., Ma, X., LoIacono, L., Beck, S.G. and Gross, C., Suppression of conditioned responses to ambiguous cues by pharmacogenetic
inhibition of dentate gyrus granule cells, Nature Neuroscience, 3 June 2007
Press Contact
Anna-Lynn Wegener
Press Officer
EMBL Heidelberg
Tel: +49 6221 387-8452
Email: wegener@embl.de |
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