Time to wake up: Studying neurovascular coupling and brain-wide circuit function in the un-anesthetized animal

• Published in: NeuroImage (Orlando, Fla.) Vol. 153; pp. 382 - 398
• Main Authors: Gao, Yu-Rong, Ma, Yuncong, Zhang, Qingguang, Winder, Aaron T., Liang, Zhifeng, Antinori, Lilith, Drew, Patrick J., Zhang, Nanyin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2017; Elsevier Limited
• Subjects: Anesthesia; Anesthetics - administration & dosage; Animal models; Animals; Awake animal; Blood; Blood flow; Brain; Brain - blood supply; Brain - drug effects; Brain - physiology; Brain Mapping; Cardiovascular system; Cerebral blood flow; Consciousness; Functional anatomy; Functional magnetic resonance imaging; Hemodynamics; Hemodynamics - drug effects; Humans; Imaging; Innovations; Magnetic Resonance Imaging; Medical imaging; Metabolism; Metabolites; Neuroimaging; Neurology; Neurosciences; Neurovascular coupling; Neurovascular Coupling - drug effects; Oxygenation; Physiology; Resonance; Reviews; Schizophrenia; Veins & arteries; Awake animal; Hemodynamics; Imaging; Neurovascular coupling
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2016.11.069

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. •We review the effects of anesthesia on neurovascular coupling and brain circuit function.•Anesthesia decreases brain metabolism and perturbs other physiological processes.•Neural excitability and neurovascular coupling are altered by anesthesia.•Brain circuit function are changed by anesthesia relative to the awake animal.•Techniques for imaging in awake rodents are presented.