June 2019

University of California, San Diego > Master’s Thesis in the field of Neuroscience (Learning & Memory)

Novel Behavioral Paradigm for Investigating Temporal Pattern Separation in Mice

Author: Emily Yan, Advisor: Matthew Shtrahman, MD/PhD, Sanford Consortium for Regenerative Medicine, La Jolla, CA

Abstract

A region of the mammalian brain called the hippocampus is crucial for memory formation. However, how the hippocampus plays a key role in encoding time-varying information is not fully understood. The hippocampus is unique because it is one of only two brain regions in mice that generate new neurons throughout life in a process known as adult neurogenesis. This peculiar anatomical feature has been hypothesized to be central to the ability of the hippocampus to make fine distinctions between similar experiences in a process known as pattern separation. New hippocampal neurons, known as newborn dentate granule cells (DGCs), are believed to play a vital role in the brain’s ability to perform pattern separation. However, DGCs rarely fire action potentials, so traditional electrophysiological techniques that depend on data collected from highly active neurons are not optimal and cannot reliably identify the rarely-firing DGCs. As a result, there are significant gaps in knowledge about how newborn DGCs contribute to the ability of the hippocampus to perform pattern separation, particularly on time-varying information. Central to this study is the optimization of a behavioral paradigm in which head-fixed mice perform a novel temporal pattern separation task that is amenable to study with two-photon calcium imaging. This study establishes a novel training protocol to allow for in-depth study of the temporal aspects of pattern separation in vivo.

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Highlights:

  • Design, prototype, and optimize a novel behavior training task for mice to study the mechanisms underlying episodic memory formation within the hippocampus, the area of the brain responsible for learning and memory.

  • Lead a multidisciplinary team of UCSD Graduate and Undergraduate students in the fields of biomedical engineering, computer science engineering, cognitive science, and physics.

  • Perform surgical techniques such as craniotomy and cranial window implantation coupled with AAV injection into the dentate gyrus of the hippocampus of mice to allow for in vivo two-photon microscopy analysis.