UCSF

Animals associate cues with outcomes and continually update these associationsas new information is presented. How might the brain allow for the learning of these associations, particularly the identity and incurred value of the cues? What might the link be between behavioral learning and neural representation? Such a complicated set of questions cannot be addressed by a single set of experiments, but the intent of this thesis is to contribute to the understanding of these foundational questions. The hippocampus is crucial for associative learning, yet how neurons track changes in cue-outcome associations remains unclear. In the experiments described in this thesis, recordings from dorsal and ventral hippocampus (vCA1 and dCA1) across days of learning in odor and tone associative learning tasks were analyzed to understand how cue and outcome representations might be differently encoded across these areas. Both areas encoded cues and outcomes, but vCA1 representations were dependent on learning and behavioral salience, while dCA1 cue representations exhibited outcome invariant stable representation. Additionally, vCA1 neurons, but not dCA1 neurons, demonstrated encoding of outcome during the odor period as well as temporally broadened encoding of outcome throughout trials. Thus, vCA1 and dCA1 appear to have diverging roles in associative learning encoding. In Chapter 1 (Introduction), I provide an introduction to the hippocampus, with special emphasis on it’s dorsal-ventral axis and potential differences in functionality. Over the last few decades, it has been increasingly hinted at that these separate areas or gradient in the hippocampus might serve overlapping but also distinct roles in various memory and learning behaviors. I will illustrate how past approaches, which have tended to focus on the spatial domain and to a lesser extent on emotion, leave many basic questions unanswered. In Chapter 2 (Neural dynamics underlying associative learning in the dorsal and ventral hippocampus), I present evidence of differences in dorsal and ventral hippocampal representations of associative learning. Using 2-photon calcium imaging, I tracked the same dCA1 and vCA1 neurons across days to determine how responses evolve across phases of odor-outcome learning. I found that, initially, odors elicited robust responses in dCA1, whereas in vCA1 odor responses primarily emerged after learning and embedded information about the paired outcome. Population dynamics in both regions rapidly reorganized with learning, then stabilized into ensembles that stored task representations for days, even after extinction or pairing with a different outcome. Finally, I found stable, robust signals across CA1 when anticipating behaviorally controlled outcomes, but not when anticipating inescapable shock. These results identify how the hippocampus encodes, stores, and updates learned associations, and illuminates the unique contributions of dorsal and ventral hippocampus. In Chapter 3 (Conclusions), I place these experimental findings within the larger context of our knowledge of the hippocampus to date. I propose that the dorsal ventral axis of the hippocampus has different roles in not only spatial learning or emotion related behavior but also associative learning and suggest further experimental studies for understanding the mechanisms underlying their differing population dynamics which could be to expand our knowledge of hippocampal function in health and disease states.