Optogenetic fMRI reveals distinct, frequency-dependent networks recruited by dorsal and intermediate hippocampus stimulations

Andrew J Weitz; Zhongnan Fang; Hyun Joo Lee; Robert S Fisher; Wesley C Smith; ManKin Choy; Jia Liu; Peter Lin; Matthew Rosenberg; Jin Hyung Lee

doi:10.1016/j.neuroimage.2014.10.039

Optogenetic fMRI reveals distinct, frequency-dependent networks recruited by dorsal and intermediate hippocampus stimulations

Neuroimage. 2015 Feb 15:107:229-241. doi: 10.1016/j.neuroimage.2014.10.039. Epub 2014 Oct 22.

Authors

Affiliations

¹ Department of Bioengineering, Stanford University, Stanford, CA 94305, USA; Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
² Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA; Department of Electrical Engineering, Stanford University, Stanford, CA 94305, USA.
³ Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305, USA.
⁴ Department of Neuroscience, University of California, Los Angeles, CA 90095, USA.
⁵ 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.
⁶ Department of Electrical Engineering, University of California, Los Angeles, CA 90095, USA; Department of Psychology, University of California, Los Angeles, CA 90095, USA.
⁷ 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.

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.

Keywords: Brain mapping; Functional MRI; Hippocampus; Optogenetics; Seizure.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Algorithms
Animals
Dentate Gyrus / physiology
Electroencephalography
Hippocampus / physiology*
Hippocampus / physiopathology
Image Processing, Computer-Assisted
Magnetic Resonance Imaging / methods*
Male
Nerve Net / physiology*
Nerve Net / physiopathology
Optogenetics / methods*
Oxygen / blood
Rats
Rats, Sprague-Dawley
Seizures / physiopathology

Substances

Oxygen

Abstract

Publication types

MeSH terms

Substances

Grants and funding