Friday, May 23, 2025
5/23/2025
Lateral habenula circuits for the regulation of goal-directed behavior - Project Summary How do we decide whether to continue pursuing a goal or abandon the quest? Survival requires both the ability to persist in behavior directed toward a goal and the ability to determine when it is time to stop, a finely-tuned balance of perseverance and disengagement. The optimal balance between goal-directed and disengaged behavior differs depending on internal state and the environment, and sensitive, context-appropriate regulation of this balance is both essential and challenging. Excessive or insufficient goal-directed behavior is associated with psychiatric dysfunction ranging from attention deficit hyperactivity disorder to obsessive compulsive disorder to addiction. Disengagement from goal pursuit is an essential process, and it can be elicited by factors with either negative or positive valence. For example, an animal might stop attempting to obtain water because its actions to obtain water have failed, because it has already consumed enough water, or because it needs to quickly respond to an imminent threat to survival. Are the circuits that suppress goal-directed behavior in response to action failure the same as those that suppress goal-directed behavior after satisfying homeostatic needs or in response to threats? The LHb is a major conduit of information from the forebrain to brainstem neuromodulatory centers, and LHb neural activity suppresses midbrain dopamine neural activity via the GABAergic rostromedial tegmental nucleus (RMTg). LHb neurons fire when animals don’t receive expected rewards and when they receive punishments, and stimulation of LHb neurons and glutamatergic inputs to the LHb promotes behavioral avoidance. The objective of this study is to systematically probe the functional role of lateral habenula (LHb) circuits in regulating disengagement from goals in response to action failure, homeostatic resolution, and threat. We will use optical methods to monitor and control LHb neural circuits in order to characterize the long-timescale dynamics and functional role of LHb neurons in regulating the balance between goal-directed and disengaged behavioral states.
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