New study uncovers brain circuits that control fear responses
Neuroscientists reveal mechanism that regulates responses to threat in
animals

Date:
October 5, 2021
Source:
Sainsbury Wellcome Centre
Summary:
Researchers have discovered a brain mechanism that enables mice
to override their instincts based on previous experience.



FULL STORY ========================================================================== Researchers at the Sainsbury Wellcome Centre have discovered a brain
mechanism that enables mice to override their instincts based on previous experience.


==========================================================================
The study, published today in Neuron, identifies a new brain circuit in
the ventral lateral geniculate nucleus (vLGN), an inhibitory structure
in the brain. The neuroscientists found that when activity in this
brain region was suppressed, animals were more likely to seek safety
and escape from perceived danger, whereas activation of vLGN neurons
completely abolished escape responses to imminent threats.

While it is normal to experience fear or anxiety in certain situations,
we can adjust our fear responses depending on our knowledge or
circumstances. For example, being woken up by loud blasts and bright
lights nearby might evoke a fear reaction. But if you have experienced fireworks before, your knowledge will likely prevent such reactions and
allow you to watch without fear. On the other hand, if you happen to be
in a war zone, your fear reaction might be strongly increased.

While many brain regions have previously been shown to be involved in processing perceived danger and mediating fear reactions, the mechanisms
of how these reactions are controlled are still unclear. Such control is crucial since its impairment can lead to anxiety disorders such as phobias
or post-traumatic stress disorders (PTSD), in which the circuits in the
brain associated with fear and anxiety are thought to become overactive, leading to pathologically increased fear responses.

The new study from the research group of Professor Sonja Hofer at the
Sainsbury Wellcome Centre at University College London, took advantage of
an established experimental paradigm in which mice escape to a shelter
in response to an overhead expanding dark shadow. This looming stimulus simulates a predator moving towards the animal from above.

The researchers found that the vLGN could control escape behaviour
depending on the animal's knowledge gained through previous experience,
and on its assessment of risk in its current environment. When mice
were not expecting a threat and felt safe, the activity of a subset of inhibitory neurons in the vLGN was high, which in turn could inhibit
threat reactions. In contrast, when mice expected danger, activity in
these neurons was low, which made the animals more likely to escape and
seek safety.

"We think the vLGN may be acting as an inhibitory gate that sets a
threshold for the sensitivity to a potentially threatening stimulus
depending on the animal's knowledge," said Alex Fratzl, PhD student in
the Hofer lab and first author of the paper.

The next piece of the puzzle the researchers are focusing on is
determining which other brain regions the vLGN interacts with to achieve
this inhibitory control of defensive reactions. They have already
identified one such brain region, the superior colliculus in the midbrain.

"We found that the vLGN specifically inhibits neurons in the superior colliculus that respond to visual threats and thereby specifically blocks
the pathway in the brain that mediates reactions to such threats --
something the animal sees that could pose a danger like an approaching predator," said Sonja Hofer, Professor at the Sainsbury Wellcome Centre
and corresponding author on the paper.

While humans do not have to worry much about predators, they also
have instinctive fear reactions in certain situations. The hope is
therefore, that clinical scientists may one day be able to ascertain if
the corresponding brain circuits in humans have a similar function, with clinical implications for the treatment of PTSD and other anxiety-related disorders in the future.

This research was supported by the Sainsbury Wellcome Centre Core
Grant from the Gatsby Charitable Foundation and the Wellcome Foundation (090843/F/09/Z), a Wellcome Investigator Award (Sonja B. Hofer) and a
Henry Wellcome Fellowship (Andre Marques-Smith).

========================================================================== Story Source: Materials provided by Sainsbury_Wellcome_Centre. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Alex Fratzl, Alice M. Koltchev, Nicole Vissers, Yu Lin Tan, Andre
Marques-Smith, A. Vanessa Stempel, Tiago Branco, Sonja
B. Hofer. Flexible inhibitory control of visually evoked defensive
behavior by the ventral lateral geniculate nucleus. Neuron, 2021;
DOI: 10.1016/ j.neuron.2021.09.003 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/10/211005124706.htm

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