They discover a new brain structure related to fear

A study reveals the key role of a brain region in fear conditioning and lays the groundwork for locating it as a therapeutic target.

The lateral habenula, a brain structure little studied so far, could play a fundamental role in the Pavlovian conditioning of fear. This is suggested by an investigation carried out by the team of Joaquín Piriz and Tomás Sachella, respectively a researcher at the National Council for Scientific and Technical Research (CONICET) at the Institute of Physiology, Molecular Biology and Neurosciences (IFIBYNE) and a scholarship holder of the Council at the Institute of Physiology and Biophysics Bernardo Houssay (IFIBIO HOUSSAY), together with a team of specialists from various scientific institutions. The results, which point to understanding the functioning of this brain structure, could contribute to advancing the treatment of pathologies associated with the expression of fear, such as phobias, anxiety disorders, post-traumatic stress, among others.

“Fear is an extreme and uncontrollable reaction to a threatening stimulus”, define the authors of the study.

There are two types of fears, those that are innate and those that can be learned. This last type of fear, and the creation of aversive memories, have been the focus of research on the role of the lateral habenula.

“The lateral habenula is known to participate in the encoding of negative events. In other words, when we don’t like something, the lateral habenula is activated”, indicates Piriz. And he continues: “We studied how this structure is related to the formation of fear memories.”

Members of the research team. (Photo: CONICET)

To achieve this, the specialists followed Pavlovian conditioning, a learning paradigm according to which “an association is produced between two stimuli,” explains Sachella. However, unlike the well-known experiment carried out by Pavlov in which he observed canine salivation in the face of a stimulus announcing food, in this case the reinforcement was negative: “The sound predicted a slight discharge”, describes Piriz.

During the training, a tone was presented to a murine model that anticipated a small electrical discharge of one second, a protocol that does not produce temporary or permanent alterations in the study subject. “Thus, the animals normally learn two things, on the one hand, that the presentation of the tone is dangerous and on the other, that the context in which they received the electric shock is also dangerous”, declares the scientist about the results of the tests. . “Two learnings that were traditionally thought of as separate”, warns Sachella about the results of the research.

In parallel, it was necessary to use pharmacological and optogenetic techniques that would temporarily activate and silence the lateral habenula during the experiments with the animal model. The aim was to assess the involvement of this brain region in conditioning.

“We found that if the lateral habenula is not present, these two learnings – about tone and context – do not occur separately, but originate together”, explains Sachella. Which suggests that the analyzed structure would participate in the conditioning of fear.

For Piriz, the lateral habenula constitutes a structure on which it is possible to act again to understand the way in which the learning mechanisms are produced, “for example in mistaken, pathological learning, of fear that are the basis of diseases such as phobias, anxiety disorders, post-traumatic stress, among others”, points out the scientist. And he adds: “Fear is generalized in such an extreme way that fear begins to appear in situations in which it should not exist, for this, potentially, it is interesting to have found a structure that regulates the generalization of fear.”

On the path traveled, scientists highlight the implementation of the Pavlovian paradigm. “It provided a clear protocol in which to look at the circuits involved in creating the aversive memory and how the lateral habenula is involved in the formation of that memory,” says Sachella.

Looking ahead, the researchers intend to continue exploring the fear generalization hypothesis and the implications of this brain structure in the process. “Incorporating it and associating it with the learning of fear could also have a translational side”, Piriz reflects on this key region of the brain. Sachella agrees: “It opens up the possibility that it could be a target for treating diseases associated with abnormalities in the expression of fear.”

The study is entitled “A novel role for the lateral habenula in fear learning”. And it has been published in the academic journal Neuropsychopharmacology. (Source: Yasmín Noel Daus / CONICET. CC BY 2.5 AR)