Discovery of novel brain fear mechanisms offers target for anxiety-
reducing drugs

Date:
March 15, 2022
Source:
University of Bristol
Summary:
A new target in the brain which underpins the eliciting of anxiety
and fear behaviors such as 'freezing' has been identified by
neuroscientists.

Researchers say the discovery of a key pathway in the brain offers
a potential new drug target for treating anxiety and psychological
disorders, which affect an estimated 264-million people worldwide.



FULL STORY ==========================================================================
A new target in the brain which underpins the eliciting of anxiety
and fear behaviours such as 'freezing' has been identified by
neuroscientists. The University of Bristol researchers say the discovery
of a key pathway in the brain, published in the journaleLife, offers
a potential new drug target for treating anxiety and psychological
disorders, which affect an estimated 264- million people worldwide.


========================================================================== Existing anxiety-reducing drugs are not always effective for all patients
and often have unwanted side effects. Understanding the brain networks
and mechanisms which underlie fear and anxiety may offer a new approach
to developing better treatments for anxiety disorders.

Neuroscientists from Bristol's School of Physiology, Pharmacology and Neuroscience, sought to investigate how the brain's cerebellum, which
is connected to many brain regions associated with survival networks, influences activity in another area of the brain called the periaqueductal
grey (PAG).

This PAG area lies at the hub of central networks that co-ordinate
survival mechanisms including fear-evoked coping responses such as
'freezing'.

To investigate this, researchers fitted animal models with electrodes to
record activity within the brain's PAG region and applied a conditioning
task, whereby an auditory tone is paired with a small foot shock,
eliciting the formation of a 'fear memory' and freezing, a behavioural
index of fear. The team showed that within the brain's PAG area, a subset
of brain cells increased their responsiveness to the conditioned tone, consistent with encoding a fear memory.

However, when cerebellar output was altered during conditioning, the
subsequent timing of fear-related neuronal activity in the PAG became
less precise and the duration of fear-related freezing behaviour was
increased confirming that cerebellar-periaqueductal grey interactions contribute to fear conditioning processes. The team showed that the manipulation of a direct cerebellar-PAG pathway, also caused impairments
in fear conditioned freezing and ultrasonic vocalisations.

The study's lead authors, Dr Charlotte Lawrenson and Dr Elena Paci,
explain: "Until now, little was understood about how the cerebellum
modulates neuronal activity in other brain regions, especially those
related to fear and anxiety.

Importantly, our results show that the cerebellum is part of the
brain's survival network that regulates fear memory processes at
multiple timescales and in multiple ways; raising the possibility that dysfunctional interactions in the brain's cerebellar-survival network may underlie fear-related disorders and comorbidities." The study's findings provide new insights into the way the PAG encodes fear memory and also
provides evidence that the cerebellum is an additional key structure in
the list of brain regions that contribute to the fear/anxiety network
and offers a novel target for treating psychological conditions including post-traumatic stress disorder.

The Biotechnology and Biological Sciences Research Council (BBSRC)
and Wellcome Trust-funded study is published in the journal eLife.


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


========================================================================== Journal Reference:
1. Elena Paci, Charlotte Lawrenson, Jasmine Pickford, Robert AR Drake,
Bridget M Lumb, Richard Apps. Cerebellar modulation of memory
encoding in the periaqueductal grey and fear behaviour. eLife,
2022; 11 DOI: 10.7554/ eLife.76278 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220315095004.htm

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