Midbrain dopamine (DA) neurons encode both reward and movement-related events, and are implicated in disorders of reward processing as well as movement. Consequently, disentangling the contribution of DA neurons in reinforcing versus generating movements is challenging and has led to lasting controversy. We dissociated these functions by parametrically varying the timing of optogenetic manipulations in a Pavlovian conditioning task, and examining the influence on anticipatory licking prior to reward delivery. Inhibiting both ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) DA neurons in the post-reward period had a significantly greater behavioral effect than inhibition in the pre-reward period of the task. Furthermore, the contribution of DA neurons to behavior decreased linearly as a function of elapsed time after reward. Together, the results indicate a temporally restricted role of DA neurons primarily related to reinforcing stimulus-reward associations, and suggest that directly generating movements is a comparatively less important function.

Fear conditioning is one of the most frequently used laboratory procedures for modeling learning and memory generally, and anxiety disorders in particular. The conditional response (CR) used in the majority of fear conditioning studies in rodents is freezing. Recently, it has been reported that under certain conditions, running, jumping or darting replaces freezing as the dominant CR. These findings raise both a critical methodological problem and an important theoretical issue. If only freezing is measured but rodents express their learning with a different response, then significant instances of learning, memory, or fear may be missed. In terms of theory, whatever conditions lead to these different behaviors may be a key to how animals transition between different defensive responses and different emotional states. In mice, we replicated these past results but along with several novel control conditions. Contrary to the prior conclusions, running and darting were primarily a result of nonassociative processes and were actually suppressed by associative learning. Darting and flight were taken to be analogous to nonassociative startle or alpha responses that are potentiated by fear. Additionally, associative processes had some impact on the topography of flight behavior. On the other hand, freezing was the purest reflection of associative learning. We also uncovered a rule that describes when these movements replace freezing: When afraid, freeze until there is a sudden novel change in stimulation, then burst into vigorous flight attempts. This rule may also govern the change from fear to panic.

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Author Contributions Section: AKR designed the studies, ran experiments, and wrote the manuscript. JCO performed electrophysiological experiments. ZP helped with optogenetic behavioral experiment analysis. FM ran VGLUT2 RNAscope experiments. SG and JT helped with optogenetic experiments. JC, NE and NK helped with behavioral experiments. WZH provided the Adcyap1-2A-Cre mice. RLN made the HSV viruses used in the intersectional viral approach. JW made and provided the PAC1 loxP/loxP and the Adcyap1-EGFP mice. BSK helped with all aspects of electrophysiological experiments and supervised JCO. The electrophysiology experiments were designed by AKR and MSF. MSF supervised all the studies and helped design the experiments and manuscript preparation.

Recent studies suggest a significant role for context in controlling the acquisition and extinction of simple operant responding. The present experiments examined the contextual control of a heterogeneous behavior chain. Rats first learned a chain in which a discriminative stimulus set the occasion for a procurement response (e.g., pulling a chain), which led to a second discriminative stimulus that occasion-set a consumption response (e.g., pressing a lever) that produced a food-pellet reinforcer. Experiment 1 showed that, after separate extinction of procurement and consumption, each response increased when it was returned to the acquisition context (ABA renewal) or was tested in a new context (AAB renewal). In addition, procurement responding, but not consumption responding, was decreased by changing the context after acquisition. Experiment 2 demonstrated ABA and AAB renewal of procurement and consumption following extinction of the whole chain. This time, the context-switch after acquisition weakened both procurement and consumption. Experiment 3 found that return to the context of the behavior chain renewed a consumption response that had been extinguished separately. Finally, in Experiment 4, rats learned two different discriminated heterogeneous chains; consumption extinguished outside its chain was only renewed on return to a chain when it was preceded by its associated procurement response. The results suggest a role for context in the extinction of chained behavior. They also support the view that procurement is influenced by the physical context and that consumption is controlled primarily by the response that precedes it in the chain.