title: Time to wake up: Studying neurovascular coupling and brain-wide circuit function in the un-anesthetized animal.
abstract: Functional magnetic resonance imaging (fMRI) has allowed the noninvasive study of task-based and resting-state brain dynamics in humans by inferring neural activity from blood-oxygenation-level dependent (BOLD) signal changes. An accurate interpretation of the hemodynamic changes that underlie fMRI signals depends on the understanding of the quantitative relationship between changes in neural activity and changes in cerebral blood flow, oxygenation and volume. While there has been extensive study of neurovascular coupling in anesthetized animal models, anesthesia causes large disruptions of brain metabolism, neural responsiveness and cardiovascular function. Here, we review work showing that neurovascular coupling and brain circuit function in the awake animal are profoundly different from those in the anesthetized state. We argue that the time is right to study neurovascular coupling and brain circuit function in the awake animal to bridge the physiological mechanisms that underlie animal and human neuroimaging signals, and to interpret them in light of underlying neural mechanisms. Lastly, we discuss recent experimental innovations that have enabled the study of neurovascular coupling and brain-wide circuit function in un-anesthetized and behaving animal models.
authors.affiliation: Neuroscience Graduate Program, Pennsylvania State University, University Park, PA 16802, Unidted States; Department of Engineering Science and Mechanics, Pennsylvania State University, University Park, PA 16802, Unidted States.
authors.forename: Yu-Rong
authors.initials: YR
authors.lastname: Gao
authors.affiliation: Department of Biomedical Engineering, Pennsylvania State University, University Park, PA 16802, Unidted States.
authors.forename: Yuncong
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Engineering Science and Mechanics, Pennsylvania State University, University Park, PA 16802, Unidted States.
authors.forename: Qingguang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Engineering Science and Mechanics, Pennsylvania State University, University Park, PA 16802, Unidted States.
authors.forename: Aaron T
authors.initials: AT
authors.lastname: Winder
authors.affiliation: Department of Biomedical Engineering, Pennsylvania State University, University Park, PA 16802, Unidted States.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Department of Biomedical Engineering, Pennsylvania State University, University Park, PA 16802, Unidted States.
authors.forename: Lilith
authors.initials: L
authors.lastname: Antinori
authors.affiliation: Neuroscience Graduate Program, Pennsylvania State University, University Park, PA 16802, Unidted States; Department of Engineering Science and Mechanics, Pennsylvania State University, University Park, PA 16802, Unidted States; Department of Neurosurgery, Pennsylvania State University, University Park, PA 16802, Unidted States; Department of Biomedical Engineering, Pennsylvania State University, University Park, PA 16802, Unidted States. Electronic address: pjd17@psu.edu.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Drew
authors.affiliation: Neuroscience Graduate Program, Pennsylvania State University, University Park, PA 16802, Unidted States; Department of Biomedical Engineering, Pennsylvania State University, University Park, PA 16802, Unidted States. Electronic address: nuz2@psu.edu.
authors.forename: Nanyin
authors.initials: N
authors.lastname: Zhang
mesh_terms: D000777:Anesthetics / Q000008:administration & dosage; D000818:Animals; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D001931:Brain Mapping; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008279:Magnetic Resonance Imaging; D000069336:Neurovascular Coupling / Q000187:drug effects
chemical_list: D000777:Anesthetics
keywords: Awake animal; Hemodynamics; Imaging; Neurovascular coupling