# Lateral habenula circuits for the regulation of goal-directed behavior

> **NIH NIH R01** · CORNELL UNIVERSITY · 2021 · $376,745

## Abstract

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.

## Key facts

- **NIH application ID:** 10280604
- **Project number:** 1R01MH127510-01
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Melissa Rhoads Warden
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $376,745
- **Award type:** 1
- **Project period:** 2021-08-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10280604

## Citation

> US National Institutes of Health, RePORTER application 10280604, Lateral habenula circuits for the regulation of goal-directed behavior (1R01MH127510-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10280604. Licensed CC0.

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