Speaker: Prof. Nashat AbumariaState Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University

Time: 13:00-14:00 p.m., Mar 25, 2025, GMT+8

Venue: Youcai Deng Lecture Hall (#101), Jin-Guang Life Science Building, PKU

Abstract: 

The ability to persist in the face of failure can help overcome challenges. However, sometimes it's advantageous to adjust our behavior, quit or give up when we face uncontrollable situations. Currently, it's unclear how the mammalian brain switches behavior in response to uncontrollability. To explore this, we developed and validated two mouse models demonstrating a transition from action to no-action during exposure to prolonged uncontrollable experiences. This switch was not due to pain desensitization or muscle fatigue, and it wasn't similar to depression / learned helplessness / anxiety / social / exploratory deficits-like behavior. Serotonin and dopamine did not modulate the behavioral transition. Instead, it's modulated by noradrenergic neurons that project to GABAergic neurons within the orbitofrontal cortex (OFC). We discovered that a reduction of norepinephrine and downregulation of alpha 1 receptor in the OFC decreased the number and activity of GABAergic neurons, which are necessary for driving action behavior via disinhibitory circuit. Our findings define a circuit that governs adaptive behavioral switches relevant to give-up-like behavior. Currently, we are establishing reward-based animal models of behavioral switch in response to uncontrollability, exploring the neural circuit regulates this switch and comparing it with that of aversive-based experience.

Source: McGovern Institute for Brain Research at PKU