Investigating distributed brain circuits in vivo with multi-axis calcium imaging
Abstract/Contents
- Abstract
- A major technological goal in neuroscience is to enable the interrogation of neural populations throughout the living brain. Calcium imaging allows monitoring of neural activity at sub-cellular resolution, but has typically been restricted to single fields-of-views per subject and hence limited to studies of local neural dynamics in isolated brain regions. Here, by combining computer-aided surgical planning for rodents, custom miniaturized optics, and specialized imaging instrumentation, we expand the capability of optical physiology to address distributed brain circuits in individual subjects. We first present the "Crystal Skull", a curved glass replacement to the dorsal mouse cranium yielding an estimated > 1 million neurons (albeit not concurrently) over > 30 neocortical areas. Next, we introduce the "multi-axis" approach for optically accessing multiple brain regions---deep or superficial---by way of a dual-axis two-photon microscope. With this apparatus, we performed, for the first time, chronic studies of the corticocerebellar pathway at single-cell resolution as mice learned a forelimb movement planning task. Concurrent optogenetic manipulation demonstrated the necessity of specific anatomical pathways for the observed corticocerebellar dynamics. This study highlights the potency of the multi-axis approach for discovering new insights for how distributed brain networks communicate and interact. From the initial dual area experiments, we identify the key optomechanical principles necessary to extend our approach to four or more regions in a single subject. Namely, scaling of the multi-axis concept requires: (1) an efficient use of the space above the animal's head by optimizing the surgical placement of optical ports (e.g. microendoscopes) on the animal itself; (2) miniaturization of each optical instrument using elements such as millimeter-scale gradient index lenses and specialized micro-prisms; and, (3) enhanced instrument maneuverability, attained by incorporating concepts such as remote center of motion from the field of surgical robotics. We design and implement a novel two-photon microscope based on these principles, which will enable the optical investigation of 4--8 brain areas simultaneously from behaving mice.
Description
| 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 | 2019; ©2019 |
| Publication date | 2019; 2019 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Kim, Hyun Tony |
|---|---|
| Degree supervisor | Schnitzer, Mark Jacob, 1970- |
| Thesis advisor | Schnitzer, Mark Jacob, 1970- |
| Thesis advisor | Nishimura, Dwight George |
| Thesis advisor | Wetzstein, Gordon |
| Degree committee member | Nishimura, Dwight George |
| Degree committee member | Wetzstein, Gordon |
| Associated with | Stanford University, Department of Electrical Engineering. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Hyun Tony Kim. |
|---|---|
| Note | Submitted to the Department of Electrical Engineering. |
| Thesis | Thesis Ph.D. Stanford University 2019. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2019 by Hyun Tony Kim
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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