Student Theses and Dissertations

Author

Andrew Toader

Date of Award

2023

Document Type

Thesis

Degree Name

Doctor of Philosophy (PhD)

RU Laboratory

Rajasethupathy Laboratory

Abstract

The hippocampus is necessary for the initial encoding and recent storage of memories. Under the standard model of systems consolidation, it is thought that the memory trace eventually reorganizes from the hippocampus to a distributed cortical network, with the anterior cingulate cortex playing a central role in remote memory retrieval. However, little is known about the mechanisms responsible for coordinating this process. Additionally, the intermediate memory representations in the brain and the circuits that might gate and select memories for permanent storage remain unknown. To facilitate the longitudinal tracking of memory circuits in the brain, we first developed a novel virtual reality-based behavioral task for mice. We used fiber photometry to record neural activity from multiple regions across the brain throughout consolidation and identified a unique and significant neural correlate of memory in anterior thalamus that emerged in training and persisted for weeks. Inhibition of the anteromedial thalamus to anterior cingulate cortex projections during training resulted in substantial memory consolidation deficits, whereas excitation of the same projection drove the consolidation of otherwise unconsolidated memories. To gain mechanistic understanding into the role of anteromedial thalamus during consolidation, we developed a technique for imaging three brain regions simultaneously with single-cell resolution in the behaving mouse. Using this technology, we uncovered that the anteromedial thalamus rapidly forms preferential tuning to consolidated memories, and establishes inter-regional correlations that are causally required for synchronizing and stabilizing cortical representations to achieve successful memory consolidation.

Comments

A Dissertation Presented to the Faculty of the David Rockefeller Graduate Program in Biosciences in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy.

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