Observational Fear as a Model of Affective Empathy in Mice

Using an observation of fear paradigm, we seek to find how the brain generates emotional contagion. In particular, we're interested in how the anterior cingulate cortex integrates multiple sensory and emotional information to induce vicarious freezing behaviors in the observer mouse. We study novel genes and underlying signaling pathways to prove synaptic and circuit dysfunctions that cause abnormal empathic ability in psychiatric disorders.

Our previous research found that somatostatin expressing interneurons in the anterior cingulate cortex bidirectionally control observational fear behaviors. Recently, we've also made further progress in understanding how specific genes regulate the functional excitation of SST neurons involved in vicarious freezing behaviors. Observational fear conditioning is advantageous as it allows the measurement of emotional contagion without subjecting the observer to direct aversive stimuli.

This process allows us to conduct multiple detailed studies on empathy-related neural circuits. This standardized animal model bridges the gap between rodent and human empathy research by providing insights into basic neural mechanisms. The model enables us to investigate both genetic factors and brain circuits involved in emotional sharing behaviors.

Using this observational fear model, we plan to investigate how the brain processes empathy. This research may reveal fundamental mechanisms that shape empathetic responses in both animals and humans. To begin, place the animals in the waiting area, along with their home cages at least 30 minutes before the procedure for acclimatization.

Assemble the apparatus for observational fear conditioning. Include two chambers partitioned by a porous, transparent plexiglass divider in the middle. Position a grid made of multiple steel rods on the chamber floor to administer electrical foot shocks.

Next, turn on the video camera and ensure that the testing chamber is fully visible within the frame for subsequent analysis. Assign one animal as the observer and the other as the demonstrator. First, place the demonstrator mouse in the chamber where the foot shock will be administered, and then position the observer mouse in the opposite chamber, separated by the divider.

Close the chamber door and immediately run the programmed protocol using the software. Allow the observer and demonstrator mice to freely move and explore in the chamber for five minutes during the habituation session. Following habituation, the system will automatically deliver electrical foot shocks to the demonstrator mouse for four minutes.

After the session, place the demonstrator and observer mice in separate holding cages. Mice in the observational fear group displayed significantly higher vicarious freezing behavior and the total freezing time during the conditioning period compared to the control group. The 129S1 mouse strain exhibited a notably higher observational fear response compared to the B6J, while the AKR mouse strain showed a significantly lower level of vicarious freezing compared to B6J.