Investigating neural substrates of generalization from past experience

点击翻译按钮获取中文摘要

PROJECT SUMMARY/ABSTRACT: In new settings, we have a remarkable ability to generalize from prior learning to help us achieve our goals. This capacity is thought to depend on our ability to represent the common relationships present in related experiences, such as the series of steps involved in grocery shopping at any one of a variety of supermarkets. These context- generalized representations of a task have been termed schemas. In the brain, schemas are thought to be represented by neural ensembles that encode a task similarly across contexts. Recent work has identified schema representations in the prefrontal cortex (PFC). How these schema representations form and support rapid learning in new contexts, however, is not well understood. A well-established theory of long-term memory formation known as systems consolidation theory provides a model for how schema representations may arise in the brain. According to this theory, the hippocampus (HPc) rapidly encodes memories of specific episodes in new contexts. In periods of rest that follow, these HPc memories are reactivated, and this is thought to result in the long-lasting strengthening of corresponding memory traces within and across neocortex. The resulting neocortical memories are thought to emphasize common features across contexts, providing a basis for schema representation. Our overarching hypothesis based on the theory of systems consolidation is that HPc memory reactivation promotes the formation of schema representations in PFC (Aims 1 and 3), and expression of these representations in new contexts in turn enables rapid learning (Aims 2 and 3). To test this hypothesis, we will pair a rat model of learning in new contexts wherein rats exhibit rapid learning given prior experience, with simultaneous recordings of PFC and HPc neural ensembles (Aims 1–3) and causal intervention studies (Aim 3). Completion of these Aims has the potential to yield fundamental insights into the neural substrates of generalization from past experience. Our findings will additionally provide important evidence for or against longstanding predictions of systems consolidation theory that have so far been difficult to test in the absence of distributed simultaneous recordings. This study will be carried out in the lab of my research sponsor, Dr. Loren Frank, at the University of California, San Francisco (UCSF). The Frank lab is located in Sandler Neurosciences Center, which is home to a highly innovative and collaborative community of faculty and students pursuing neuroscience questions. My training plan under this fellowship will prepare me for an independent career as an academic physician scientist with the long-term goal of revealing neural computations underlying cognitive processes. In addition to the proposed research, this preparation will be achieved through rigorous quantitative coursework, planned engagement with vibrant intellectual communities, and clinically geared activities.