Anna Gillespie is a postdoctoral researcher in Loren Frank’s lab at the University of California, San Francisco (UCSF). She earned her B.S. in biology from Stanford University in 2010, and received her Ph.D. in biomedical sciences from UCSF in 2015. During her graduate work in Yadong Huang’s lab at the Gladstone Institute of Neurological Disease, Gillespie identified abnormalities in hippocampal network activity caused by apolipoprotein E4, the major genetic risk factor for Alzheimer’s disease. Intrigued by the relationships between cellular pathology, network dysfunction and cognitive performance, Gillespie ultimately plans to use in vivo extracellular recording techniques to better understand how changes in network activity lead to cognitive decline in models of neurological disease. She hopes to use this understanding to develop and apply network-scale manipulations to alleviate or even prevent disease symptoms. In the Frank Lab, she is working toward this goal by developing techniques to modulate physiologically relevant patterns of activity in the hippocampus.
Project: “Modulating hippocampal replay to better understand memory-guided behavior”
Our everyday lives are constantly influenced by our prior experiences, which are stored as memories and conjured up at critical points to guide our decisions. This process of consolidating and retrieving memories depends heavily on the hippocampus and is thought to involve a phenomenon called hippocampal replay. During replay, the hippocampus activates a compressed version of the neural activity pattern that occurred during an experience, and this repetition is thought to be critical for consolidating memory. Though replay often occurs during sleep, it can also occur during pauses in awake behavior. Some evidence suggests that awake replay may not only consolidate recent experience but may also allow stored memories to inform ongoing planning and decision-making.
We don’t yet understand what information is represented during awake replay, or how that information might be used. Does it provide information about the past to help guide decisions, or represent planning for action once a decision has been made? Could enhancing replay improve performance on a memory-based task, or influence subsequent behavior? In order to answer these questions, we need a way to selectively promote replay. Gillespie has therefore developed a paradigm that allows me to change the prevalence of hippocampal replay. She records activity from place cells in the hippocampus, which allows her to detect replay events and decode the experiences that they represent. Over the course of training, rats can learn to increase the occurrence of replay events during a memory-dependent task. Using this paradigm, she is currently examining how the content of the replay events relates to the rat’s behavior — for instance, whether the replay reflects where the animal came from or where it plans to go next. In the future, she plans to assess whether promoting replay can improve memory in rodent models of neurological disease.