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What’s safe, what’s not? a single brain cell decides

New breakthrough study by TIFR can help design new treatments against post-traumatic stress disorders

Tata Institute of Fundamental Research in Mumbai. (Source: Express photo)
Tata Institute of Fundamental Research in Mumbai. (Source: Express photo)

Terror attacks, war, natural disasters, sexual assault, serious injuries and even bullying in adults or children can lead to anxiety disorders, known as post-traumatic stress disorders (PTSD). Now, researchers from the Tata Institute of Fundamental Research’s (TIFR’s) National Centre for Biological Sciences (NCBS) have discovered how the brain’s ability to distinguish safe from dangerous can go badly wrong, potentially leading to a state of generalised fear. Excess generalisation of the original fearful stimulus is a key symptom of PTSD.

The breakthrough findings reveal, for the first time, that the loss of one’s ability to determine what is safe and what is dangerous can happen at the level of a single brain cell. Their findings, published in the journal, “Nature Neuroscience”, can help in designing new treatments against PTSD.

“Psychiatric disorders like PTSD is a debilitating disorder triggered by a traumatic or life-threatening experience. In addition to repeated flashbacks, patients respond with intense fear and hyperarousal, similar to that experienced during the original traumatic event, reacting to things which pose no threat. Excessive generalisation of the original fearful stimulus is a major symptom of PTSD,” said NCBS professor Sumantra Chattarji, senior author of the study.

According to the findings of the fear-conditioning experiments, done with live rats, individual neurons in the emotional hub of the brain called the amygdala, which were initially capable of telling the difference between safe from dangerous stimuli, can start firing indiscriminately, causing one to become fearful of non-threatening situations.


“Fear memories are crucial for survival, but problems arise when one loses the ability to distinguish between what’s safe and what’s dangerous and starts fearing things which he or she should not. While we have known that the amygdala, a brain structure that forms memories of fearful experiences, becomes hyperactive in PTSD, how and why this happened was not known before. Our study shows that loss of ability to distinguish between what’s safe and what’s not can happen at the level of an individual brain cell and hence, it’s a very fine balance. Further, we have identified a specific biochemical signalling mechanism inside amygdala neurons that can cause this transition to generalised fear, which could potentially serve as a target for designing new treatments against PTSD,” said Chattarji.

In the experiment, rats were exposed to two distinctly different sounds, one was paired with a mild electric shock, while the other was not.

Thus, one tone predicted danger and another was “safe”. The rats quickly learned to discriminate between the two. As the animals learned, the researchers recorded electrical signals from individual neurons. These recordings revealed that the amygdala neurons fired more electrical signals in response to the dangerous tone, thus mirroring the animal’s behaviour. The authors also noticed that a small number of neurons did not possess this ability and fired indiscriminately to both tones.

“Strikingly, when the shock associated with the dangerous tone increased, the same animals lost their ability to discriminate between the two stimuli and started fearing the safe tone too. The proportion of brain cells, which could not understand what’s safe and what’s unsafe, now went up by five or six times. Thus, a much larger proportion of amygdala neurons lost their ability to discriminate and fired signals indiscriminately,” he added.

The study reveals that the same neuron, which was initially capable of discriminating safe from dangerous, lost its ability to do so when the animal exhibited generalised fear and reflected the animal’s tendency to play it safe.

“Accordingly, the animals acted as if potential danger lurked behind the safe tone too. It is this abnormal response that pushes one towards anxiety disorders,” said Chattarji.