Cognition, Behavior, and Memory
Author: Sol Bencardino | Email: sbencardino@gmail.com
Sol Bencardino1°2°, M. Paula Ospital1°3°, Joaquín Piriz1°
1° Instituto de Fisiología, Biología Molecular y Neurociencias (IFIByNE, UBA-CONICET)
2° Facultad de Ciencias Exactas y Naturales (FCEN-UBA)
Fear, characterized by the perception of risk, serves as an adaptive survival mechanism. However, its dysregulation can lead to anxiety disorders, phobias, and post-traumatic stress disorder. The lateral habenula (LHb) plays a key role in encoding aversive memories. Fear conditioning (FC) is one of the most commonly used protocols to study these types of memories, where a neutral element or conditioned stimulus (CS) is paired with an aversive unconditioned stimulus (US). We developed an FC protocol to investigate fear generalization in mice—defined as the extension of fear from a stimulus associated with an aversive experience to other, similar stimuli. We then used fiber photometry to measure calcium activity in LHb neurons, aiming to understand the role of this structure in the generalization process.
Our results show that the intensity of the aversive stimulus is a critical factor in fear generalization. We successfully established two distinct groups: a “Strong Shock” group, which exhibited fear generalization to both the cue and the context, and a “Weak Shock” group, which showed associative learning without generalization. This distinction is essential for differentiating between generalized and specific fear responses. Moreover, we observed LHb activation in response to the conditioned stimulus, suggesting its role in encoding aversiveness and predicting the CS. These findings offer insights into fear generalization, crucial for developing targeted therapies.