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Effects of inactivation of the lateral habenula on effort-based decisions in rats

The lateral habenula (LHb) has been associated with depression. One symptom of depression that is particularly associated with quality of life is lack of motivation. Several lines of evidence point to the LHb possibly mediating effort-based decisions pointing to a role in mediating these symptoms. In order to examine this, we implemented an effort-based task, where the rats chose between making an effortful decision to climb over a barrier to receive a high reward versus a low reward without a barrier (two versus one sugar pellet, respectively). Specifically, a plus-maze, with dimensions of 10x15x30 cm, was used where north and south were designated as the high or low arm, east and west were designated as start arms. The first few stages allowed the rat to explore the maze, associate sugar pellets with rewards, and become familiar with a block in a designated arm. Rats then learned that the high arm is worth two pellets while the low arm other is worth one, while the opposite stem arm was blocked. The high and low reward arms remained constant, but the stem arms would vary pseudorandomly. Once the reward conditions were learned, the next stage consisted of barriers of increasing sizes (small, medium, large), the barrier made the high arm reward more effortful. The rats had to reach the criteria of >80% for all barriers to be ready for surgery, meaning they had to choose the high arm >80% of the time out of thirty trials. In surgery, a cannula was then implanted into their LHb. Once the rat recovered from surgery, the sequence of injection (ABBA) began with 50 ng Muscimol (B) or saline solution (A). Preliminary results suggest that inactivation of the LHb alters choice behavior on the task. Overall, these results indicate that the LHb mediates effort-based decisions possibly related to dysfunction in choice behaviors in depression.