Date of Award
Doctor of Philosophy (PhD)
The N-methyl-D-aspartate receptor (NMDAR) plays a variety of important roles in the development and function of primate central nervous systems. This thesis describes three nonhuman primate studies that, together, demonstrate that pharmacologically reducing NMDAR activity not only causes dramatic changes in neural activity in cortex, but also changes the relationship between that activity and a key signal often used as its proxy in human studies, the blood-oxygen-level-dependent (BOLD) signal. The first study reveals that NMDA antagonism is sufficient to induce powerful low-frequency modulation of spiking activity and extracellular local field potential (LFP) and discusses the implications of this finding for the role of NMDA hypofunction in the physiological, dissociative and anesthetic effects of the non-selective NMDA antagonist ketamine. The second study provides evidence that neurovascular coupling between cortical spiking activity and tissue oxygenation gives rise to an important component of the BOLD signal fluctuations underlying resting-state functional connectivity. The third study demonstrates that NMDA antagonism suppresses spike-oxygen coupling, and discusses the implications of this finding for BOLD studies involving NMDA antagonists. A concluding chapter discusses possible approaches to blocking spike-oxygen coupling without the dramatic changes to cortical activity seen under NMDAR antagonists.
Chair and Committee
Acland, Benjamin Thomas, "The Effects of NMDA Antagonism on Neuronal Activity and Neurovascular Coupling in Non-Human Primate Cortex" (2022). Arts & Sciences Electronic Theses and Dissertations. 2768.
Available for download on Saturday, August 05, 2023