Stress is an inevitable part of life, and while it can be temporary, for many individuals, it can result in profound, long-lasting changes in behavior and mental health. In recent years, much attention has been devoted to understanding how the brain processes and responds to stress, particularly in relation to disorders like post-traumatic stress disorder (PTSD). Although much is known about how traumatic memories are encoded in the brain, little has been understood about the long-term neural changes that occur after a stressful event, particularly those that influence emotional and behavioral responses well after the trauma has occurred.
Recent research from the Laboratory of Thalamus Research at the HUN-REN Institute of Experimental Medicine has shed light on a significant, previously unexplored aspect of stress-induced neural changes. Using a rodent model, the team discovered a sustained increase in neural activity in a specific part of the brain known as the paraventricular thalamus (PVT) that persisted for several days following exposure to a strong stressor. These findings, published in PLOS Biology, could have significant implications for understanding and treating stress-related disorders, such as PTSD, anxiety, and sleep disturbances.
The Discovery: Prolonged Changes in Neural Activity
The researchers used a rodent model to investigate the brain’s response to stress. They exposed the mice to an ecologically relevant stressor—the scent of a predator (fox)—for a short period of 10 minutes. This stressor was chosen because it triggers acute stress disorder-like symptoms in mice, similar to those seen in humans, such as increased arousal, negative mood, and sleep disturbances.
What the researchers discovered was groundbreaking. After the stressful event, there was a prolonged elevation of neural activity in the PVT, a nucleus in the thalamus that plays a key role in processing stress, motivation, and alertness. The heightened activity persisted for several days, even though the stressor had been removed. This sustained neural activity in the PVT was associated with several behavioral symptoms, including restlessness during wakefulness, disturbed behavior before sleep, and prolonged sleep onset. These behaviors are commonly seen in individuals with PTSD and other stress-related disorders.
However, the researchers found that the heightened neural activity could be reversed. When they selectively inhibited the PVT activity for just one hour after the stressor, the sustained increase in activity did not occur, and the behavior of the mice returned to normal. This suggests that modulating PVT activity could potentially help prevent or alleviate the long-term behavioral effects of a stressful event.
A New Understanding of Brain Response to Stress
The phenomenon of prolonged elevated neural activity is especially intriguing because it goes against the usual patterns of brain activity regulation. In the brain, there are typically robust mechanisms that work to counter excessive excitatory activity. When neurons fire too frequently, compensatory mechanisms often increase inhibitory activity to restore balance. Even in cases of epilepsy, where there are abnormal bursts of activity in the brain, the periods between seizures usually exhibit normal neural activity due to this compensatory inhibition.
However, the findings of this study reveal that under certain circumstances and in specific brain regions, this typical inhibitory response may be insufficient. The PVT appears to be a special case where neural activity can remain elevated for prolonged periods, even after the stressor has ended. This suggests that the PVT is uniquely poised to alter brain state long after a single stressor, which could have profound implications for our understanding of stress and its long-term effects on behavior.
The Role of the PVT: A Key Hub for Stress and Behavior
The PVT is a relatively small, but critically important, cluster of neurons located in the thalamus, a part of the brain that acts as a relay station for sensory information. The PVT is particularly interesting because it integrates inputs from various brain regions that are involved in stress, motivation, and alertness. It then relays this integrated information to major brain regions, such as the prefrontal cortex, amygdala, hippocampus, and nucleus accumbens—all of which are involved in controlling behavior.
The PVT’s unique organization allows it to act as a bottleneck, where signals from multiple brain areas converge and are transmitted to the rest of the forebrain. This makes the PVT a crucial player in integrating stress signals and relaying them to regions of the brain that control behavioral responses. Notably, no other brain region is known to have the same network of connections, making the PVT a central hub in the brain’s stress response.
Earlier research from the same team demonstrated that the organization of the PVT is strikingly similar in both mice and humans. This is significant because it suggests that the PVT’s role in stress processing and behavioral regulation is evolutionarily conserved across species. This raises the possibility that the PVT could be a central target for therapeutic interventions aimed at treating stress-related disorders in humans.
Implications for Treating Stress and PTSD
The implications of these findings for understanding and treating stress-related disorders, such as PTSD, are profound. PTSD is a debilitating condition that can arise after a person experiences or witnesses a traumatic event. It is characterized by intrusive memories, avoidance behaviors, emotional numbness, and hyperarousal. A key feature of PTSD is the persistent recurrence of traumatic memories, even in the absence of direct reminders of the trauma. Additionally, individuals with PTSD often experience disturbed sleep patterns, difficulty concentrating, and emotional instability.
While much research has focused on the mechanisms involved in memory formation and memory retrieval in PTSD, less is understood about how the brain maintains these emotional and behavioral changes over time. The findings from this study suggest that the persistent changes in neural activity following a stressful event may not be related to the memory trace itself, but rather to an independent mechanism that alters brain activity in response to the stressor.
This insight could be crucial for developing new therapeutic strategies for treating stress-related disorders. Currently, the main treatments for PTSD focus on extinguishing memories through exposure therapy or pharmacological interventions. However, these treatments are often not fully effective, and they do not address the underlying changes in brain activity that contribute to the persistence of PTSD symptoms. By modulating PVT activity, researchers may be able to develop treatments that target the long-term neural changes triggered by stress, offering a new avenue for intervention.
Therapeutic Potential: A Window for Intervention
One of the most exciting aspects of this research is the discovery that the sustained increase in PVT activity can be reversed. The researchers found that a one-hour inhibition of PVT activity was sufficient to prevent the prolonged elevation of neural activity, and this inhibition remained effective even when applied five days after the stressor. This suggests that PVT modulation could be a promising therapeutic strategy for alleviating the long-term effects of stress, even in cases where the individual has already experienced a significant traumatic event.
The finding that the therapeutic window for intervention could last for days after the stressful event is particularly encouraging. It suggests that treatments based on modulating PVT activity could be effective not only in the acute phase following a trauma but also in the chronic phase when symptoms of stress and PTSD may persist for months or even years.
Concluding Thoughts: A New Era in Stress Research and Treatment
This groundbreaking research offers new insights into how the brain responds to stress and how these responses can lead to long-term behavioral changes. The discovery of sustained, persistent changes in PVT activity provides a novel mechanism by which the brain alters its state following exposure to a stressful event. These findings open up exciting possibilities for developing new treatments for stress-induced anxiety, PTSD, and other stress-related disorders.
By targeting the PVT and modulating its activity, it may be possible to alleviate the long-term effects of stress, providing a much-needed therapeutic strategy for individuals who suffer from chronic stress-related conditions. As research in this area progresses, we may be on the cusp of a new era in the treatment of stress and trauma, one that focuses on restoring neural balance rather than simply extinguishing memories or symptoms.
Reference: Anna Jász et al, Persistently increased post-stress activity of paraventricular thalamic neurons is essential for the emergence of stress-induced alterations in behaviour, PLOS Biology (2025). DOI: 10.1371/journal.pbio.3002962