The goal of this project is to provide the building blocks for an independent research program focused on the neural basis of long-term memory formation across distributed hippocampal-cortical networks. In humans, removal of the hippocampus and its associated structures leads to permanent anterograde amnesia, and hippocampal damage is believed to underlie the memory impairments of early Alzheimer's disease. As hippocampal neurons, known as place cells, fire in specific locations of the environment (place fields), spatial navigation in the hippocampus is one of the most prominent models for studying memory processes. Importantly, place cells replay previous activity patterns in a compressed manner during offline periods such as sleep and rest. These reactivations occur during network events called sharp wave ripple oscillations (SWRs), and are thought to strengthen the connections between neurons that encoded the initial experience, both within the hippocampal network and in cortical regions. This project will test the hypothesis that SWRs are responsible for plasticity in the intra- and extra- hippocampal networks. First, it will determine whether SWRs support the modification of place field locations that has been shown during spatial learning, as well as memory performance. Preliminary data based on closed-loop optogenetic manipulations indicate that indeed, SWRs are involved in the consolidation of the spatial representation during spatial learning. The second part of this proposal focuses on memory consolidation at the system level and is aimed at determining whether SWRs support the learning of an odor association, by favoring plasticity the piriform cortex. To achieve these goals, Dr. Roux will perform high density neuronal recordings combined with advanced closed-loop optogenetic methods in the hippocampus and piriform cortex of freely moving rodents. The technical and scientific skills that Dr. Roux will develop during the training period of this projet will not only be crucial for the accomplishment of her immediate scientific goals, they will also become the pillars for the research she will develop in her own independent laboratory in the field of olfaction. This training will be complemented by intense carrier developmental activities and mentorship that will prepare her for the practical aspects of laboratory management, teaching and fund raising. Overall, Dr. Roux's current and future research will provide new insights into the neural mechanisms involved in memory formation. Knowing that hippocampal damage is believed to underlie the memory impairments of early Alzheimer's disease, and that replay activity during SWRs is impaired in a model of schizophrenia, such knowledge may have important clinical relevance.

Public Health Relevance

The goal of this project is to address the crucial question of how memory traces are encoded in the hippocampus and across brain regions. It will directly test the impact of the most synchronous activity pattern described in the healthy brain on in vivo neural network plasticity and memory formation. These findings will be important not only for understanding the physiological basis of memory processes, but also relevant to human brain disorders, such as Alzheimer's disease.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Career Transition Award (K99)
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NST-2 Subcommittee (NST)
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Babcock, Debra J
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New York University
Schools of Medicine
New York
United States
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Roux, Lisa; Hu, Bo; Eichler, Ronny et al. (2017) Sharp wave ripples during learning stabilize the hippocampal spatial map. Nat Neurosci 20:845-853