Raül Andero Galí: Neural Pathways and Translational Mechanisms in Fear Memory

Raül Andero Galí (Institute of Neuroscience, Autonomous University of Barcelona): 
Neural Pathways and Translational Mechanisms in Fear Memory

Abstract: It remains unexplored in the field of fear memory whether functional neuronal connectivity between two brain areas is necessary for one sex but not the other. Chemogenetic silencing of centromedial (CeM)-Tac2 fibers in the lateral posterior BNST (BNSTpl) decreased fear memory consolidation in male mice but not females. Optogenetic excitation of CeM-Tac2 fibers in the BNSTpl exhibited enhanced inhibitory postsynaptic currents in males compared to females, with in vivo calcium imaging revealing a sex-dimorphic fear memory engram in the BNSTpl. Furthermore, in humans, the single-nucleotide polymorphism (SNP) in the Tac2 receptor (rs2765) (TAC3R) decreased CeM-BNST connectivity in a fear task, impaired fear memory consolidation, and increased the expression of the TAC3R mRNA in AA-carrier men but not in women. These sex differences in critical neuronal circuits underlying fear memory formation may be relevant to human neuropsychiatric disorders with fear memory alterations, such as posttraumatic stress disorder. Additionally, exposure to traumatic stress can lead to fear dysregulation, which has been associated with Posttraumatic stress disorder (PTSD), particularly in women with the PACAP-PAC1R (pituitary adenylate cyclase-activating polypeptide) system polymorphism. Mice subjected to acute stress immobilization exhibited fear extinction impairments, associated with changes in Adcyap1 and Adcyap1r1 mRNA expression in the hypothalamus, and were treated with corticosterone to prevent a PTSD-like phenotype, including anxiety-like behavior, depression-like behavior, and social behavior.

For more information, please see the lab website: https://www.anderolab.com/