Abstract

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.

Committee Chair

Camillo Padoa-Schioppa

Committee Members

Steven Petersen

Comments

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Degree

Doctor of Philosophy (PhD)

Author's Department

Biology & Biomedical Sciences (Neurosciences)

Author's School

Graduate School of Arts and Sciences

Document Type

Dissertation

Date of Award

Winter 12-15-2022

Language

English (en)

Author's ORCID

http://orcid.org/0000-0001-6392-6634

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