TEMPORAL ROLES OF VTA DOPAMINE NEURONS IN FEAR LEARNING, EXTINCTION, AND POST-LEARNING SLEEP

Dopamine plays a central role in fear learning and extinction, yet its contribution depends strongly on the timing of dopaminergic engagement and the strategies used to manipulate neuronal activity. While inhibition of ventral tegmental area (VTA) dopamine neurons during extinction, particularly at shock omission, has been reported relatively consistently across studies using different optogenetic tools, their role during fear acquisition remains more heterogeneous. Here, we examine the contribution of VTA dopamine neuron activity to cue-based fear conditioning, extinction, and post-conditioning sleep using temporally precise optogenetic inhibition. We manipulated VTA dopamine neurons during defined behavioral epochs, including shock delivery during conditioning and shock omission during extinction, and compared inhibitory opsins with distinct biophysical properties (iC++ and NpHR). The chloride-conducting opsin iC++, which more closely preserves physiological ionic gradients, has so far been little used in fear conditioning paradigms targeting VTA dopamine neurons. Preliminary observations suggest that inhibition during fear acquisition can influence subsequent extinction across multiple days, whereas effects during extinction itself appear more robust across optogenetic strategies, in line with prior work. In parallel, we are investigating whether VTA dopamine neuron activity during post-conditioning sleep, particularly REM sleep, contributes to offline processing of fear memories, an aspect that remains largely unexplored. Together, this work emphasizes the importance of temporal specificity when interpreting dopaminergic contributions to fear memory across waking behavior and sleep.