International acclaim bestowed upon studies of the neural pathways that process fear

Nature Reviews Neuroscience dedicated its cover to studies funded by FAPESP and conducted by the USP’s Biomedical Sciences Institute. Scientists showed that the neural processing of distinct types of fear involves different paths in the brain.

By Fábio de Castro

Agência FAPESP – Studies conducted in the last few years by Brazilian and American researchers have shown that contrary to what was previously believed, different types of fear – such as fear of pain, fear of natural predators and fear of more aggressive members of the same species – are processed by independent neural circuits.

In addition to distinguishing the neural pathways for processing “instinctive fears” and the different types of “learned fears” in rats, the researchers also discovered that these different pathways are found in humans. Based on this finding, future studies may contribute to a better understanding of problems such as panic attacks and post-traumatic stress.

Coordinated by Newton Canteras of the Functional Neuroanatomy Laboratory of Universidade de São Paulo’s Biomedical Sciences Institute (ICB-USP) and funded in part through a FAPESP Thematic Project, “Neural basis of motivated behavior,” these studies on fear were the cover story of the September edition of Nature Reviews Neuroscience.

According to Canteras, the studies conducted in rats at ICB-USP were based on an induced “instinctive fear” stimulus, which is characterized as a survival mechanism, and on “learned fears,” which are cultural and are acquired over a lifetime.

“One of the important points highlighted in the article was the discovery that in rodents, the circuit related to the threat of a natural predator can also be activated in human beings when facing life-threatening events. This discovery could help us to understand situations such as post-traumatic stress,” said Canteras in an interview with Agência FAPESP.

According to Canteras, when this topic was first studied by his group in 1995, the predominant theory in the scientific community was that fear responses were organized in a unitary fashion in the nervous system.

“This process was discovered based on experiments that associate a painful stimulus,  such as a shock, for example, and a sound or a specific environment. After being submitted to this association several times, the animal exhibited fear when exposed to the sound or environment, even without the painful stimulus. This experiment was thought to be sufficient to fully explain the reaction of fear,” he explains.

However, when USP researchers began to study the neural system that is involved in natural fear situations, they realized that the mechanisms were not as simple as they seemed.

“When we tested the exposure of rodents to a cat, which is its natural predator, we discovered that the fear response activated a completely different cerebral region than a simple pain stimulus. Based on this, we spent several years conducting studies focused on more precisely reproducing natural fears,” said Canteras.

According to Canteras, an animal is built so that it has a fear reaction when it is exposed to something that threatens its life. The innate fear reactions are split into two categories: predatory threats – which occur in the presence of a predator – and social threats, which are threats caused by an aggressive animal of the same species.

“The animal does not learn this type of fear – it is an innate reaction. We discovered that there was not just a distinction between the neural pathways activated for innate fear reactions and learned fear reactions – which is the case for the pain stimulus – but that the fear caused by a predator and the fear caused by social threats also use different pathways in the brain,” he explains.   

According to Canteras, the discoveries were considered important because a series of human pathologies derive from fear, such as anxiety, panic attacks and post-traumatic stress disorder.

“The fact that there are distinct neural pathways for processing fear has several consequences. An individual who has been electrically shocked does not panic when he or she sees a socket later. However, someone who has been assaulted ends up having a panic reaction after being submitted to stimuli associated with that event,” he stated.

Understanding the neural system used in each situation will help us to understand how learned fear responses are organized. “The neural pathways of learned fear are related to human pathologies,” he said.

According to Canteras, in 2010, scientists discovered that the stimulus of the nucleus of the hypothalamus – a region necessary for rats to manifest fear of predators – involves a circuit that also exists in humans and that could possibly be activated in a life-threatening situation.

“The system in rats that is involved in detecting threats to life, such as the presence of predators, is also found in humans. The fact that there are parallels gives us the prospect of developing approaches to understand how these mechanisms are organized in the human brain,” he declares.

The article The Many Paths to Fear by Newton Canteras and Cornelius Gross can be read by subscribers of Nature Reviews Neuroscience at www.nature.com/nrn/journal/v13/n9/full/nrn3301.html.