Healthcare, UK (Commonwealth Union) – Post-Traumatic Stress Disorder (PTSD) is a mental health condition that can develop after experiencing or witnessing a traumatic event. It is characterized by a range of symptoms, including flashbacks, nightmares, severe anxiety, and uncontrollable thoughts about the event. Although PTSD is commonly associated with military combat, it can also result from a variety of traumatic experiences, such as sexual assault, physical abuse, natural disasters, or even life-threatening illnesses.
While the symptoms of PTSD can be challenging to manage, effective treatments are available, and recovery is possible with the right support and resources. By raising awareness and understanding of PTSD, can lead to help break the stigma surrounding mental health and encourage those affected by this disorder to seek the help they need to heal and move forward.
Neuroscientists at UCL have identified the brain’s response to threats, which facilitates escape, when necessary, in a recent mouse study.
These discoveries could pave the way for developing new treatments for anxiety and PTSD.
Published recently in Current Biology, the study conducted by researchers at the Sainsbury Wellcome Centre at UCL focuses on a brain region called the periaqueductal gray (PAG). This area is known to be overactive in individuals with anxiety and PTSD. The research revealed that inhibitory neurons in the PAG are continuously active, allowing their activity levels to be adjusted. This modulation directly influences escape initiation in mice, and the same neurons also determine the duration of escape behaviors.
Professor Tiago Branco, Group Leader at the Sainsbury Wellcome Centre at UCL and the corresponding author of the study, pointed out that escape behavior is not fixed – it’s adaptable with experience. Our previous research showed that mice are more or less likely to escape based on their past experiences. We aimed to understand how the brain modulates sensitivity to threats, as this insight could have significant implications for individuals with anxiety and PTSD, where these neural circuits might be dysregulated.
To understand how the brain governs escape behavior, the researchers initially conducted recordings from PAG inhibitory neurons in vitro (in a dish) to examine their characteristics. They discovered that in the absence of external input, these neurons consistently fire. This observation was validated through live animal recordings using calcium imaging and head-mounted miniature microscopes while mice moved around. Additionally, connectivity studies in the brain demonstrated that PAG inhibitory neurons have direct connections to excitatory neurons responsible for commencing escape.
Professor Branco stated that they observed that the entire escape network is under direct inhibitory control. During escape, a group of cells showed reduced activity just before the escape began, indicating that the inhibition was lifted to initiate escape. Another group of cells exhibited gradually increasing inhibition as the animal escaped, peaking when the animal reached safety. This suggests that inhibitory cells not only control escape initiation but also signal the animal to stop upon coming to safety.
To further investigate, the team employed optogenetics, a technique that allows precise manipulation of neuron activity by exciting or inhibiting them. When they artificially increased the activity of PAG inhibitory neurons, the likelihood of escape decreased. Conversely, when they inhibited these neurons, the escape probability increased. This confirmed that PAG inhibitory neurons function as a dial, modulating the animal’s sensitivity to threats.
Professor Branco says “To check whether these neurons are also important for controlling when escape stops, we first activated the neurons after the animals had started escaping and found that they stop before they reach the shelter. Then when we inhibited the neurons, we found that mice run past the shelter and do not stop escaping. This means the neurons have access to the information that the animal uses to know when it has reached safety.”
The next objective for the team is to comprehend how the perception of threat influences the system’s excitability by engaging these neurons.
Professor Branco further added “If we were able to reveal the specific molecular pathway that links experience to the recruitment of these neurons, then it is conceivable that drugs could be developed to target this pathway so that the sensitivity could be dialled up or down in people with anxiety and PTSD.”
This research received backing from the Wellcome, the Gatsby Charitable Foundation, and the European Research Council, with additional support from the German Research Foundation and the Max Planck Society.
