title: Optogenetic fMRI reveals distinct, frequency-dependent networks recruited by dorsal and intermediate hippocampus stimulations.
abstract: Although the connectivity of hippocampal circuits has been extensively studied, the way in which these connections give rise to large-scale dynamic network activity remains unknown. Here, we used optogenetic fMRI to visualize the brain network dynamics evoked by different frequencies of stimulation of two distinct neuronal populations within dorsal and intermediate hippocampus. Stimulation of excitatory cells in intermediate hippocampus caused widespread cortical and subcortical recruitment at high frequencies, whereas stimulation in dorsal hippocampus led to activity primarily restricted to hippocampus across all frequencies tested. Sustained hippocampal responses evoked during high-frequency stimulation of either location predicted seizure-like afterdischarges in video-EEG experiments, while the widespread activation evoked by high-frequency stimulation of intermediate hippocampus predicted behavioral seizures. A negative BOLD signal observed in dentate gyrus during dorsal, but not intermediate, hippocampus stimulation is proposed to underlie the mechanism for these differences. Collectively, our results provide insight into the dynamic function of hippocampal networks and their role in seizures.
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Weitz
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA; Department of Electrical Engineering, Stanford University, Stanford, CA 94305, USA.
authors.forename: Zhongnan
authors.initials: Z
authors.lastname: Fang
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Fisher
authors.affiliation: Department of Neuroscience, University of California, Los Angeles, CA 90095, USA.
authors.forename: Wesley C
authors.initials: WC
authors.lastname: Smith
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
authors.forename: ManKin
authors.initials: M
authors.lastname: Choy
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA; Department of Neuroscience, University of California, Los Angeles, CA 90095, USA; Department of Electrical Engineering, University of California, Los Angeles, CA 90095, USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Lin
authors.affiliation: Department of Electrical Engineering, University of California, Los Angeles, CA 90095, USA; Department of Psychology, University of California, Los Angeles, CA 90095, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Rosenberg
authors.affiliation: Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA; Department of Electrical Engineering, Stanford University, Stanford, CA 94305, USA; Department of Neurosurgery, Stanford, CA 94305, USA. Electronic address: ljinhy@stanford.edu.
authors.forename: Jin Hyung
authors.initials: JH
authors.lastname: Lee
mesh_terms: D000465:Algorithms; D000818:Animals; D018891:Dentate Gyrus / Q000502:physiology; D004569:Electroencephalography; D006624:Hippocampus / Q000502:physiology* / Q000503:physiopathology; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009415:Nerve Net / Q000502:physiology* / Q000503:physiopathology; D062308:Optogenetics / Q000379:methods*; D010100:Oxygen / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000503:physiopathology
chemical_list: D010100:Oxygen
keywords: Brain mapping; Functional MRI; Hippocampus; Optogenetics; Seizure