How neuroscientists are detangling the fear response

BioTechniques News
Jade Parker

Individuals who have experienced life-threatening, stressful situations can later be prone to showing a fear response in the absence of a threat. This is called a generalized fear response and now scientists have mapped the neural circuitry underlying it.

Our brains are evolutionarily hardwired to sense fear. However, what happens when this response is triggered in the absence of threat? The mechanisms underlying this generalized stress-induced fear response have remained unknown until now. Researchers at the University of California, San Diego (CA, USA), have uncovered the stress-induced biochemical changes and neural circuitry responsible for causing our brains to present a generalized fear response.

Following a particularly stressful or life-threatening situation, an individual may display fear in situations that aren’t threatening. This generalized fear response can be psychologically damaging and could potentially lead to long-term mental health conditions, like PTSD.

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The current study sought to identify the neurotransmitters responsible for the generalized fear response. Studying the dorsal raphe in mouse brains, the team discovered that stress caused changes in the chemical signals of the neurons, switching excitatory ‘glutamate’ to inhibitory ‘GABA’ neurotransmitters, leading to generalized fear responses.

To further explore this switch, the team studied postmortem human brains of individuals who had PTSD. They again observed this glutamate-to-GABA neurotransmitter switch. By uncovering this form of brain plasticity, the researchers then investigated how they could stop it. Prior to inducing stress, they injected adeno-associated virus into the dorsal raphe of the mice with the aim of suppressing the gene responsible for GABA synthesis. This prevented the generalized fear response in mice.

Taking it one step further, mice treated with fluoxetine – an antidepressant – immediately following the stressful event showed no generalized fear response and transmitter switching was prevented.  In addition to these treatment experiments, the team mapped the neurons that were undergoing transmitter switches and showed that they were indeed connected to other regions of the brain that have previously been implicated in fear.

As demonstrated, this research can be utilized to develop interventions that are targeted, enhancing their efficacy.

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