title: Mapping the functional network of medial prefrontal cortex by combining optogenetics and fMRI in awake rats.
abstract: The medial prefrontal cortex (mPFC) plays a critical role in multiple cognitive and limbic functions. Given its vital importance, investigating the function of individual mPFC circuits in animal models has provided critical insight into the neural basis underlying different behaviors and psychiatric conditions. However, our knowledge regarding the mPFC whole-brain network stays largely at the anatomical level, while the functional network of mPFC, which can be dynamic in different conditions or following manipulations, remains elusive especially in awake rodents. Here we combined optogenetic stimulation and functional magnetic resonance imaging (opto-fMRI) to reveal the network of brain regions functionally activated by mPFC outputs in awake rodents. Our data showed significant increases in blood-oxygenation-level dependent (BOLD) signals in prefrontal, striatal and limbic regions when mPFC was optically stimulated. This activation pattern was robust, reproducible, and did not depend on the stimulation period in awake rats. BOLD signals, however, were substantially reduced when animals were anesthetized. In addition, regional brain activation showing increased BOLD signals during mPFC stimulation was corroborated by electrophysiological recordings. These results expand the applicability of the opto-fMRI approach from sensorimotor processing to cognition-related networks in awake rodents. Importantly, it may help elucidate the circuit mechanisms underlying numerous mPFC-related functions and behaviors that need to be assessed in the awake state.
authors.affiliation: Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA 16802, USA; Center for Neural Engineering, The Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USA.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Neural and Behavioral Sciences, College of Medicine, The Pennsylvania State University, Hershey PA 17033, USA; Center for Neural Engineering, The Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USA.
authors.forename: Glenn D R
authors.initials: GD
authors.lastname: Watson
authors.affiliation: Neural and Behavioral Sciences, College of Medicine, The Pennsylvania State University, Hershey PA 17033, USA; Center for Neural Engineering, The Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USA.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Alloway
authors.affiliation: Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Gangchea
authors.initials: G
authors.lastname: Lee
authors.affiliation: Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA 16802, USA; Center for Neural Engineering, The Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Neuberger
authors.affiliation: Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA 16802, USA; Center for Neural Engineering, The Huck Institutes of Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USA. Electronic address: nuz2@psu.edu.
authors.forename: Nanyin
authors.initials: N
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001931:Brain Mapping; D003342:Corpus Striatum / Q000502:physiology; D008032:Limbic System / Q000502:physiology; D008279:Magnetic Resonance Imaging; D008297:Male; D009415:Nerve Net / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D062308:Optogenetics; D017397:Prefrontal Cortex / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D015203:Reproducibility of Results
keywords: Awake; Medial prefrontal cortex; Opto-fMRI; Rat