Neural mechanisms of memory consolidation in the hippocampus and medial prefrontal cortex

Memory is an essential cognitive process dependent on the consolidation of experience into stored memories and generalized knowledge. We know not all memories are stored, and we know memories undergo a transformation from episodic events into abstract understanding. However, the neural underpinnings of this process of memory consolidation remain unclear. The hippocampus is a brain region critical for memory formation, and the medial prefrontal cortex (mPFC) is a brain region involved in memory storage and abstracted knowledge; these regions are bidirectionally connected and are candidate brain networks for the selection of memories for consolidation and the transformation of memory traces into generalized knowledge. Further, the sleep sharp-wave ripple (SWR) is a brain oscillation known to be involved in memory consolidation during which privileged hippocampal-mPFC communication occurs. While systems consolidation theory offers predictions of how the hippocampus and mPFC interact during SWRs to consolidate memories, these predictions have so far been difficult to causally test in the absence of multi-site neural recordings with optogenetic manipulations. To test the hypothesis that cortical-hippocampal information flow preceding SWRs is critical for the selection of memories for consolidation, this project aims to silence mPFC activity in conjunction with simultaneous large- scale electrophysiology recording of the hippocampus. This will determine the role of the mPFC in influencing hippocampal activity during SWRs, providing a mechanism by which memory traces are selected for consolidation (Aim 1). In addition, to test the hypothesis that hippocampal-cortical information flow during SWRs is critical for the emergence of consolidated, generalized cortical representations, I will specifically inhibit mPFC activity during SWRs. This will evaluate whether mPFC activity during this brain oscillation is necessary for the transformation of memory traces and the development of neural representations of generalized knowledge (Aim 2). Completion of these aims has the potential to yield fundamental insights into the neural mechanisms of memory consolidation. This study will be carried out in the lab of research sponsor, Dr. Loren Frank, at the University of California, San Francisco (UCSF). The Frank Lab is located in the Sandler Neurosciences Center, which is home to a highly innovative and collaborative community of faculty and students pursuing neuroscience investigation. Pursuing this project will accomplish the training goals of gaining expertise in in vivo electrophysiology data acquisition, developing quantitative data analysis skills, and improving my scientific communication. The training plan under this fellowship will provide preparation for an independent career as an academic neuroscientist-neurologist with the long-term goal of revealing neural circuits underlying cognitive processes and flexible behavior. In addition to the proposed research, this preparation will be achieved via composition of scientific manuscripts, engagement with vibrant intellectual communities, and neurology-geared clinical activities. Project Number: 1F30MH144874-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Mental Health (NIMH) | Principal Investigator: Denisse Morales-Rodriguez | Institution: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, SAN FRANCISCO, CA | Award Amount: $50,078 | Activity Code: F30 | Study Section: Special Emphasis Panel[ZRG1 F01B-G (20)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11388697