Project 462542

Although decades of investigations have pinpointed the function of the dentate gyrus (DG) of the hippocampus in supporting memory, the neurobiological mechanisms underlying specific cognitive functions, such as pattern separation, remain elusive. Pattern separation describes the ability to dissociate very similar memories (i.e. "where did I park my car yesterday" versus "where did I park my car today"). Although these two events share many similarities, the brain must encode these events as unique and distinct events to support accurate memory retrieval. The DG is known to support pattern separation, yet how changes in DG neural firing patterns underlie the ability to perform pattern separation remains unknown. Using a combination of cutting-edge tools such as in vivo calcium imaging coupled with chemogenetics in behaving animals, the project aims to 1) identify how neurons in the hippocampus decorrelate similar information to support pattern separation, 2) determine the role that DG neurogenesis - the continual birth of new neurons - plays in this decorrelation process. Initial results show that decorrelation is mediated by changes to the firing rates and temporal co-activity patterns in the hippocampus, and that decorrelation is dependent on adult born neurons in the DG. Further analysis shows evidence of both spatial and object coding in a pattern separation task. This has motivated further exploration of the spatial and non-spatial inputs to the DG, which arrive from the medial entorhinal (MEC) and lateral entorhinal cortex (LEC), respectively. We hypothesize that MEC inputs underlie hippocampal rate changes and LEC input underlies the changes in hippocampal temporal co-activity that support behavioral pattern separation. Together, these experiments will provide some of the first insights into how entorhinal and hippocampal circuits produce the neural activity patterns necessary to support behavioral pattern separation.