Research Uncovers Link Between Stress and Unlearned Fear Responses

Stress can significantly alter an organism’s response to perceived threats, as new research reveals that it primes certain neural pathways, leading to heightened fear reactions. A collaborative study conducted by scientists at the University of Texas, Austin, and the University of California, Los Angeles, has identified mechanisms in the brain that trigger this stress-enhanced fear response (SEFR) when exposed to new, unrelated fear cues.

The phenomenon of stress-induced reactions has been a part of survival strategies for living beings throughout history. When faced with a perceived threat, creatures typically enter a state of hyper-alertness, diverting bodily functions away from non-essential tasks to prepare for a “fight or flight” response. While this mechanism is beneficial for immediate survival, it can lead to long-term changes in how individuals react to various threats.

Researchers highlighted a critical aspect of SEFR, noting its connection to anxiety disorders, phobias, and post-traumatic stress disorder (PTSD). Significant insights into this relationship emerged from a series of experiments conducted on mice, shedding light on the brain’s role in unlearned fear responses.

Experimental Findings Reveal Neural Mechanisms

In their experimental setup, the research team confined lab mice in a conditioning chamber, an aluminum box measuring approximately one foot on each side. Mice in the control group remained undisturbed, while those in the stress group received mild electrical footshocks at random intervals. Subsequently, both groups were placed in the same chamber without receiving shocks, allowing the team to observe the mice’s behavior.

The stress-conditioned mice displayed an automatic freezing response in the familiar environment, becoming immobile and hyper-alert. This reaction is instinctive, particularly for prey animals like mice, which rely on freezing as a strategy to avoid detection by predators. Even when introduced to a different chamber with new auditory stimuli, the stressed mice exhibited heightened freezing behavior, indicating the presence of SEFR.

Interestingly, the stress group mice only froze in response to the audio tones, suggesting that their fear response had not generalized to the new context, but rather remained specific to the stimuli presented.

Insights into the Brain’s Role in Fear Responses

To explore the underlying mechanisms of unlearned fear, the scientists examined the brains of the stressed mice for a protein known as c-fos, which signals brain cells to activate. They discovered increased levels of c-fos in a specific area of the brain called the paraventricular thalamus (PVT) following exposure to the audio cues, but only in those mice that had previously experienced footshocks. This finding indicates that the unlearned fear response is linked to heightened activity in the PVT.

The PVT plays a crucial role in processing sensory information and relaying it to other brain regions. The researchers verified their findings by injecting a calcium-sensing protein into the PVT, which illuminated active neurons during the unlearned fear response. When the activity of these neurons was inhibited, the stressed mice did not exhibit freezing behavior in response to the audio tones, demonstrating that the PVT’s activation is integral to SEFR while leaving learned fear responses unaffected.

Dr. Reeteka Sud, a neuroscientist and senior scientist at the Center for Brain and Mind, Department of Psychiatry at NIMHANS in Bengaluru, emphasized the significance of these findings. The study not only enhances the understanding of how stress influences fear responses but also opens new avenues for treatment options for conditions such as PTSD.

The research, published in March 2024, underscores the complex interplay between stress and fear, highlighting the need for further exploration of the PVT’s role in unlearned fear responses. This knowledge could ultimately lead to improved clinical interventions for individuals suffering from anxiety and trauma-related disorders.