Neural mechanisms underlying spatial navigation and memory
Abstract/Contents
- Abstract
- An animal's survival depends intimately on its ability to navigate the environment. While the neural processes underlying spatial navigation have long intrigued scientists, only recently have we begun to understand how external sensory inputs are integrated into a mental representation of space. In the first of three sections in this thesis, I introduce two of the main classes of cells fundamental to generating this internal map: 'place cells' in the hippocampus and 'grid cells' in the medial entorhinal cortex. The discoveries of each cell type brought about experimental and computational efforts to uncover the mechanisms underlying their precise spatial coding. In the first section of Chapter 1, I review recent discoveries into the mechanisms governing the formation of place cells, while focusing in particular on the role of input from grid cells to provide background for my main experimental project, detailed in Chapter 2. Additionally, I hope to bring a new perspective into discussions of place cell formation by highlighting how newly discovered heterogeneity in the genetic profiles, biophysical properties and connectivity of hippocampal pyramidal neurons supports place cells' diverse functional coding properties. I then describe the prevailing model of grid cell formation and recent experimental manipulations probing the role of grid cells in behavior to provide context for the insights into these topics uncovered by my own experimental findings. Chapter 2 contains the primary research project that I conducted during my Doctoral training. This work involves several components, each of which make new contributions to the topics outlined above. First, using a combination of electrophysiological recordings and a viral-mediated knockout strategy, I determined that the scale of grid cell representations is modulated by HCN1 channels in the entorhinal cortex. This discovery has key implications for models of grid cell formation. Moreover, it afforded me the unique opportunity to investigate the roles of grid scale in downstream hippocampal place coding and spatial memory. I found that specifically increasing grid scale leads to parallel increase in the scale of place cell representations. While prominent models of place cell formation had long predicted this result, demonstrating it conclusively was only made possible by the discovery of a means to alter grid scale without impacting other types of spatially modulated cells. Surprisingly, increasing grid scale also reduced the long-term stability of place maps. In this chapter I describe the results from a computational model that we developed to help explain mechanistically how grid scale may play this unexpected role. I also describe the impact of increasing grid and place representations on a behavioral task requiring the formation of new place memories across days. Lastly, in a final section (Chapter 3), I discuss insights gained from my experimental findings and future directions that arise from the work presented in this dissertation.
Description
| Alternative title | Neural mechanisms underling spatial navigation and memory |
|---|---|
| Type of resource | text |
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2018; ©2018 |
| Publication date | 2018; 2018 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Mallory, Caitlin Sierra |
|---|---|
| Degree supervisor | Giocomo, Lisa |
| Thesis advisor | Giocomo, Lisa |
| Thesis advisor | Hestrin, Shaul |
| Thesis advisor | Huguenard, John |
| Thesis advisor | Raymond, Jennifer L |
| Degree committee member | Hestrin, Shaul |
| Degree committee member | Huguenard, John |
| Degree committee member | Raymond, Jennifer L |
| Associated with | Stanford University, Neurosciences Program. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Caitlin Sierra Mallory. |
|---|---|
| Note | Submitted to the Neurosciences Program. |
| Thesis | Thesis Ph.D. Stanford University 2018. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2018 by Caitlin Sierra Mallory
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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