Survival depends on the selection of behaviors adaptive for the current environment. For example, a mouse should run from a rapidly looming hawk but should freeze if the hawk is coasting across the sky. Although serotonin has been implicated in adaptive behavior, environmental regulation of its functional role remains poorly understood. We found that stimulation of dorsal raphe serotonin neurons suppressed movement in low- and moderate-threat environments but induced escape behavior in high-threat environments, and that movement-related dorsal raphe serotonin neural dynamics inverted in high-threat environments. Stimulation of dorsal raphe GABA neurons promoted movement in negative but not positive environments, and movement-related GABA neural dynamics inverted between positive and negative environments. Thus, dorsal raphe circuits switch between distinct operational modes to promote environment-specific adaptive behaviors.

This review, one of a series of articles, tries to make sense of optogenetics, a recently developed technology that can be used to control the activity of genetically-defined neurons with light. Cells are first genetically engineered to express a light-sensitive opsin, which is typically an ion channel, pump, or G protein–coupled receptor. When engineered cells are then illuminated with light of the correct frequency, opsin-bound retinal undergoes a conformational change that leads to channel opening or pump activation, cell depolarization or hyperpolarization, and neural activation or silencing. Since the advent of optogenetics, many different opsin variants have been discovered or engineered, and it is now possible to stimulate or inhibit neuronal activity or intracellular signaling pathways on fast or slow timescales with a variety of different wavelengths of light. Optogenetics has been successfully employed to enhance our understanding of the neural circuit dysfunction underlying mood disorders, addiction, and Parkinson’s disease, and has enabled us to achieve a better understanding of the neural circuits mediating normal behavior. It has revolutionized the field of neuroscience, and has enabled a new generation of experiments that probe the causal roles of specific neural circuit components.

Journeys to novel and familiar destinations employ different navigational strategies. The 1 first drive to a new restaurant relies on map-based planning, but after repeated trips the 2 drive is automatic and guided by local environmental cues 1,2 . Ventral striatal dopamine rises 3 during navigation toward goals and reflects the spatial proximity and value of goals 3 , but the 4 impact of experience, the neural mechanisms, and the functional significance of dopamine 5 ramps are unknown 4,5 . Here, we used fiber photometry [6][7][8] to record the evolution of activity 6 in midbrain dopamine neurons as mice learned a variety of reward-seeking tasks, starting 7 recordings before training had commenced and continuing daily for weeks. When mice 8 navigated through space toward a goal, robust ramping activity in dopamine neurons 9 appeared immediately -after the first rewarded trial on the first training day in completely 10 naïve animals. In this task spatial cues were available to guide behavior, and although ramps 11 were strong at first, they gradually faded away as training progressed. If instead mice 12 learned to run a fixed distance on a stationary wheel for reward, a task that required an 13 internal model of progress toward the goal, strong dopamine ramps persisted indefinitely. 14 In a passive task in which a visible cue and reward moved together toward the mouse, ramps 15 appeared and then faded over several days, but in an otherwise identical task with a 16 stationary cue and reward ramps never appeared. Our findings provide strong evidence that 17 ramping activity in midbrain dopamine neurons reflects the use of a cognitive map 9,10 -an 18 internal model of the distance already covered and the remaining distance until the goal is 19 reached. We hypothesize that dopamine ramps may be used to reinforce locations on the way 20 to newly-discovered rewards in order to build a graded ventral striatal value landscape for 21 guiding routine spatial behavior.The decision to continue pursuing a goal or abandon the quest depends on how much progress has 1 been made, how much remains to be done, and the value of the goal. For example, a climber will 2 be more deterred by rain at a mountain's base than near the summit, and will be more reluctant to 3 abandon a prized peak than a training hill. Information about progress toward goals and their value 4 is essential for adaptively balancing time and energy between activities, and commitment to goals 5 and the vigour of goal-directed actions are both regulated by goal progress and value 11-16 . 6 7Ventral striatal dopamine (DA) progressively rises as rodents navigate toward spatially distant 8 rewards 3 , a surprising recent finding that was not anticipated by temporal difference learning 9 models of DA function 4 but which has broadened our understanding of the role of ventral striatal 10 DA in sustaining and invigorating goal-directed behavior 17 . DA ramps reflect the value and 11 proximity of goals, scaling by the value of the reward and stretching or compressing in ...