Fear is an emotion that we experience when we face real or imagined danger. The formation of the basis of what is known as fear memory involves various neural circuits that are responsible for the encoding, storage and retrieval of environmental signals that predict threats. However, the neurobiology underlying these processes is not well understood.
Now, researchers from the Translational Mechanisms of Fear Memory Lab at the Institute of Neurociències (INc-UAB) have carried out a study in which they describe the detection of new neural circuits involved in fear memory that differ in men and women. These findings have been published in the journal Science Advances and have profound implications for understanding human neuropsychiatric disorders, such as post-traumatic stress disorder (PTSD), in which alterations occur in fear memory.
Sex differences in the consolidation of fear memory
The scientists explored the role of a neural pathway called Tac2 and the functional connectivity of two different brain areas: the centromedial amygdala and the bed nucleus of the stria terminalis. Using chemogenetics, optogenetics, electrophysiology, and in vivo calcium imaging techniques in freely moving mice (with miniscopes), they were able to manipulate and observe these neural circuits in mice, showing that functional connectivity between the centromedial amygdala and the bed nucleus of the stria terminalis is critical for fear memory consolidation in male, but not in female, mice.
To corroborate this phenomenon in healthy humans, they analyzed data from functional magnetic resonance imaging, postmortem brain tissue, and a fear task in men and women taking into account a certain genetic variation of the Tac2 receptor. The results showed that this genetic variation reduces the functional connectivity between these two brain areas, demonstrating that memory consolidation when performing a fear task was impaired in men, but not in women.
The knowledge gained from this research could help find more effective solutions and personalized therapies to address neuropsychiatric disorders.
These findings, based on previous research conducted by the same group led by ICREA research professor Raül Andero, from INc-UAB, who identified sex-specific effects of Tac2 in the centromedial amygdala, are relevant for developing therapies for neuropsychiatric disorders with fear memory alterations, such as post-traumatic stress disorder.
The study also addresses the underrepresentation of female samples in preclinical research and aims to close the gap in understanding sex differences in fear memory processing, both at the molecular and behavioural levels. The insights gained from this research could help to find more effective solutions and personalised therapies to address neuropsychiatric disorders.
Source: Autonomous University of Barcelona (UAB)
