A recent auditory memory requires the hippocampus for recall;however, this memory eventually becomes hippocampus-independent and consolidated in auditory cortex. Interactions between the hippocampus and cortex during sleep are thought to be critical for this process of memory consolidation. One potential mechanism by which information can be transferred between hippocampus and cortex is replay, a phenomenon where neural ensembles encoding an experience are spontaneously reactivated in hippocampus and cortex while the subject is sleeping. Cortico-hippocampal replay provides a powerful model to study memory, providing a means to decode the content of the memory being reactivated and transferred. Previous research studying replay has only focused on how spatial information related to navigation is encoded into memory. I plan to apply this replay-based model of memory consolidation to the auditory system to study how auditory memories are encoded in auditory cortex. My research plan is divided into three main aims: 1) examining the causal relationship between hippocampal replay and the memory consolidation of auditory cues in a spatial context, 2) understanding how auditory cortical activity during sleep influences what memories are replayed by the hippocampus, and 3) studying how hippocampal replay transfers and encodes new auditory memories in auditory cortex. I will adapt recording methodologies currently used in the hippocampus (multi-tetrode microdrive arrays) for the auditory cortex of freely moving rodents. In addition, I will adapt a recently developed method of reversible neural inactivation called DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) for auditory cortex. This method has the advantage of being able to target neurons genetically and can be activated non-invasively (ligand can be taken orally or through an IP injection). During the training period of this award, under the close mentorship of Matthew Wilson, I intend to learn to use two new methodologies: building a multi-site microdrive array and inactivation of neural circuits using DREADDs. I also plan to develop two new tools- a staggered stereotrode probe and laminar-specific reversible inactivation. I plan to accomplish these goals, complete and publish the first aim of this research proposal, and apply for faculty positions within 12-18 months. After obtaining a faculty position, I will transition to the independent components of the award, where I will setup my own laboratory, complete and publish the remaining aims of this research proposal, and begin to study the encoding of auditory objects in auditory cortex (during both perception and memory consolidation). Matthew and I have explicitly discussed these research and career goals, and I have his complete support during the mentored phase of my research plan. Matthew Wilson's laboratory is well-funded, and there are ample resources and facilities within the Picower Institute and Department of Brain and Cognitive Sciences to aid me in my pursuit of my research and career goals.
Auditory cortex and the hippocampus are two regions of the brain that are important for remembering a previously heard sound. Investigating how these two brain areas interact with each other will help provide a better understanding of the neural mechanisms responsible for memory storage in the brain. This research will also improve our understanding of brain disorders with cortico-hippocampal dysfunction, such as Alzheimer's disease and Schizophrenia.