Abstract of Funded Project Novelty and surprise have long been known to facilitate learning and memory. At a functional level this makes sense; unexpected events have to be learned about so they can be predicted and responded to appropriately in the future. At a psychological level, surprising events have been shown to enhance memory because they induce rehearsal. Subjects tend to “think about” unexpected events more than familiar ones after they occur. This has been observed directly in humans (explicit rehearsal) and indirectly in animals (implicit rehearsal). In both cases, the memory enhancement can be eliminated by disrupting rehearsal with a distractor stimulus that is presented immediately after the novel event. Presenting the same distractor stimulus several minutes later has no eGect. This suggests rehearsal is short-lasting and distinct from the process of memory consolidation, which stabilizes new information for several hours after learning. In addition to increasing rehearsal, novel events also trigger the release of norepinephrine (NE) and dopamine (DA), which are known to enhance synaptic plasticity. Blocking receptors for these neuromodulators in the hippocampus prevents animals from forming new spatial and contextual memories. Based on these findings, we hypothesize that surprising events enhance memory because they induce catecholamine release at the same time the hippocampus is actively rehearsing/replaying new information. Our preliminary data demonstrate that NE and DA are both released in the hippocampus during and after the presentation of an unexpected aversive stimulus. At the same time, there is an increase in sharp-wave ripple oscillations (SWRs), which are known to contain replay sequences for recently encountered stimuli. Consequently, we will test the hypothesis above by monitoring and manipulating catecholamine release in real-time during an aversive learning task while simultaneously recording oscillations and single unit activity in the hippocampus. Abstract of Proposed Research Project Savannah is a third year Neuroscience graduate student who started working in my lab in March, 2023. She arrived with experience performing behavioral assays in mice, but little experience imaging and manipulating neural activity in vivo. During the training period, Savannah will use fiber photometry and optogenetic techniques to monitor and manipulate the activity of dopaminergic neurons in the VTA during an aversive learning task that depends in the hippocampus (trace fear conditioning). In previous studies (proposed in the parent RO1), we used these techniques to image activity and induce DA release in the hippocampus by stimulating LC neurons during trace fear conditioning. This work revealed that the LC was the primary source of the observed DA signal in dorsal CA1 during aversive learning. It also showed that DA functioned as a salience signal and did not appear to convey information about prediction errors. In addition to the ...