2024-04-07 14:07:25
When we feel threatened or in a risk situation, the nervous system activates fear, an essential defense mechanism that warns us that we may be in danger and puts us on alert. But sometimes fear arises without any tangible threats.
Episodes of severe or life-threatening stress can induce fear, even in situations that are not a real threat, but experiencing this generalization of fear is psychologically harmful and, over time, can lead to mental disorders such as posttraumatic stress (PTSD).
Now, a team of neurobiologists from the University of California (United States) has identified the changes in brain biochemistry that induce fear in the absence of threats and has mapped the neural circuits that cause the experience of generalized fear.
The research, published this Thursday in the journal “Science”, provides new knowledge about how fear responses could be prevented.
The work, led by Hui-quan Li, who conducted the research at UC (he is now at the pharmaceutical laboratory Neurocrine Biosciences) and Nick Spitzer, professor at the UC School of Biological Sciences, describes the research on which it is based the discovery of neurotransmitters – the chemical messengers that allow neurons in the brain to communicate with each other – that are at the basis of generalized fear induced by stress.
Studying an area of the brain called the dorsal raphe (in the brain stem) in mice, they discovered that acute stress induced a change in the chemical signals of neurons, switching from the excitatory neurotransmitters “glutamate” to the inhibitory “GABA”, which caused widespread fear.
“The advantage of understanding these processes at this level of molecular detail – what happens and where it happens – allows for targeted intervention in the mechanism driving related disorders,” says Spitzer.
Following the discovery, the team examined postmortem human brains from individuals who had suffered PTSD, and confirmed a similar switch from the neurotransmitter glutamate to the neurotransmitter GABA.
Next, they found a way to stop the production of generalized fear: Before experiencing acute stress, they injected the mice’s dorsal raphe with an adeno-associated virus (AAV) to suppress the gene responsible for GABA synthesis, which prevented the mice from felt general fear.
Furthermore, when mice were treated with the antidepressant fluoxetine (Prozac) immediately after a stressful event, transmitter switching and the subsequent onset of generalized fear were prevented.
The team not only identified the location of the neurons that switched their transmitter, but they demonstrated the connections of these neurons with the central amygdala and lateral hypothalamus, brain regions that have previously been linked to the generation of other fear responses.
“Now that we know the core of the mechanism by which stress-induced fear occurs and the circuits that put it into practice, interventions can be selective and specific,” emphasizes Spitzer.