RT Journal Article SR Electronic T1 Title: Time to wake up: Studying neurovascular coupling and brain-wide circuit function in the un-anesthetized animal JF bioRxiv FD Cold Spring Harbor Laboratory SP 077024 DO 10.1101/077024 A1 Yu-Rong Gao A1 Yuncong Ma A1 Qingguang Zhang A1 Aaron T. Winder A1 Zhifeng Liang A1 Lilith Antinori A1 Patrick J. Drew A1 Nanyin Zhang YR 2016 UL http://biorxiv.org/content/early/2016/09/25/077024.abstract AB 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.