Striking an adaptive balance between persistently pursuing goals and reacting quickly to important environmental events is essential for survival. 

Here, I will discuss the role of neuromodulation in regulating this balance, and I will describe our recent work on this topic using optical methods to monitor and control the activity of serotonin and dopamine neurons and their inputs in freely behaving mice. 

First, I will present evidence that phasic activity in dorsal raphe serotonin neurons promotes a fast, state-dependent behavioral/emotional reaction, and will discuss the implications of this finding for the therapeutic efficacy of drugs that target the serotonin system. Then, I will present evidence that progressively rising activity in ventral tegmental area dopamine neurons during approach to rewards signifies the use of an internal model of progress toward a goal. Finally, I will present our recent findings that lateral habenula tonic activity serves as a neutral valence brake on reward-seeking behavior.