Methodology and Applications of Functional MRI in the Non-anesthetized Rat

Open Access
- Author:
- Cramer, Samuel
- Graduate Program:
- Neuroscience
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- September 30, 2024
- Committee Members:
- Patrick Drew, Outside Unit Member
Paul Bartell, Major Field Member
Nanyin Zhang, Chair & Dissertation Advisor
Thomas Neuberger, Outside Field Member
Helen Kamens, Major Field Member
Sonia Cavigelli, Program Head/Chair - Keywords:
- Awake Animal fMRI
MRI
BOLD fMRI
Interoception
Stress
Non-anesthetized
Awake Rat fMRI - Abstract:
- The topics of this dissertation relate to awake rat fMRI. Awake rat fMRI is a fairly modern neuroscience methodology, first appearing as recently as 1998. The backbone of this methodology is functional magnetic resonance imaging, which is a specialized technique developed during the late 1980s and a direct descendent of the more general technique magnetic resonance imaging. Magnetic resonance imaging itself emerged in the late 1970s as the culminating, technological achievement of many Noble laureates whose contributions stem from theoretical advances in nuclear magnetic resonance. Simply put, awake rat fMRI is an imaging application with a rich and involved history, downstream from decades of seminal breakthroughs in physics, engineering, chemistry, and biology dating back to the late 1930s. In Chapter 1 of this dissertation, starting with a formal treatment of systems neuroscience, the origins of functional magnetic resonance imaging are chronologically detailed in order to equip the reader with an adequate knowledge foundation. Further, condensed timelines of other relevant technologies like electroencephalography, electrophysiology, and positron emission tomography are reviewed to provide the appropriate motivation behind functional magnetic resonance imaging’s utilization in neuroscience research. The chapter concludes with accessible descriptions of the neurovascular coupling and blood oxygenation level-dependent contrast theories that form the basis of most awake rat fMRI studies. In Chapter 2, the groundwork for awake rat fMRI paradigms is introduced by focusing on the animal-tailored, sensory-evoked protocols that were developed in anesthetized animals between 1993 and 1997. The advent and early years of awake animal fMRI are then thoroughly chronicled, establishing the general approaches that must be employed in order to adapt the functional magnetic resonance technique to awake rats. These approaches predominantly included customized body and head restraint devices. Subsequent sections detail the personal designs developed to accommodate a diverse set of imaging experiments ranging from pupil monitoring to simultaneous electrophysiology-fMRI. Meticulous descriptions of head post implantation surgeries are also supplied, characterizing innovative strategies to avoid accompanying imaging artifacts. In Chapter 3, a select collection of restraint and acoustic noise stress studies are reviewed. Their intimate relationship with awake rat fMRI is then discussed in the context of stress habituation paradigms aimed at reducing the potential confounding influences of stress on functional datasets. An independent evaluation of an awake rat fMRI acclimation protocol is then detailed, ultimately indicating that the classical strategies used to mitigate stress confounds may be inadequate. Finally, Chapter 4 showcases a novel application of awake rat fMRI that permits the exploration of interoceptive phenomena. Briefly, a surgically implanted gastric balloon was used to cyclically induce distension of a non-anesthetized rat’s stomach during simultaneous BOLD fMRI. The study revealed widespread BOLD activations in the inferior colliculus, cerebellum, ventral midbrain, and a variety of hippocampal structures. A brief supplementary Chapter 5 brings this dissertation to a close. Within this chapter, opinions are offered regarding the current perceived weaknesses of the awake animal fMRI field, as well as fMRI techniques more generally. Suggestions for improvement are offered, and desires for future directions are expressed.