HUN-REN IEM Researchers Uncover New Neurological Foundations of Stress-Related Behavioural Changes

An assault in the street, an accident, a family tragedy, or an ordeal in war – around 20% of individuals who experience such events show lasting changes in behaviour. Researchers distinguish between the early, acute phase (up to 30 days after the stressor) and the later phase (after 30 days, in cases of post-traumatic stress disorder, PTSD). Symptoms are similar in both phases. One of the best-known symptoms of PTSD is the frequent recurrence of traumatic memories in inappropriate situations. Less well known is the fact that, in addition to intermittent symptoms, there can be persistent ones that significantly affect mood and behaviour. Naturally, the severity of these symptoms varies between individuals. Examples of such symptoms include restlessness, difficulty falling asleep, emotional instability, and withdrawal.

Although many studies investigate how the brain encodes and retrieves memories, it remains unclear which neural processes underlie the long-lasting emotional changes associated with them. Researchers know that during the encoding and retrieval of memories, brief changes occur in the activity of the groups of neurons that store these memories. However, when the event is not recalled, the brain's memory trace remains in a 'dormant' state: neural activity is low and unchanged. According to the researchers, it is therefore unclear how these brief fluctuations in activity related to memories can lead to persistent emotional states, particularly in the days following stressful events. This is a crucial question because current main treatments for PTSD focus on extinguishing memories, but these approaches are not very effective.

In an experiment using a rodent stress model, researchers at HUN-REN IEM discovered a sustained increase in neural activity that persisted for several days after a stressful event. This is significant because the brain typically has robust mechanisms to reduce excessive activity, making it previously unknown that such prolonged, sustained activity could exist.

In the experiment, stress was induced in the mice by the scent of a predator (fox), to which they were exposed for 10 minutes. Following the stressor, the researchers observed increased neuronal activity in the animals, which was accompanied by restlessness during wakefulness, disturbed behaviour during sleep, and prolonged sleep onset. The heightened activity was recorded in the paraventricular nucleus (PVT), a uniquely organised cluster of neurons in the thalamus. This was no coincidence: the PVT acts as a "hub" where signals from brain areas encoding stress and alertness converge before being relayed to the cortex, which regulates behaviour.

The researchers then selectively inhibited PVT cells for one hour and found that the sustained increase in PVT activity did not occur. This was accompanied by an absence of stress-induced behavioural changes that normally persist for several days. Interestingly, the short, one-hour PVT inhibition remained significantly effective even when applied five days after the stressful event. This finding extends the potential time window in which a treatment based on these findings could be effective.

The results highlight a new brain mechanism responsible for stress-induced behavioural changes. This mechanism could pave the way for new therapies for treating stress-related issues. By permanently modulating PVT activity, treatments could be developed that effectively address stress-induced anxiety and trauma-related disorders. A deeper understanding of these long-term neural changes could also contribute to the development of targeted therapies aimed at alleviating stress-related behavioural disorders.