ISMRM 24th Annual Meeting & Exhibition • 07-13 May 2016 • Singapore

Scientific Session: fMRI Basic Neuroscience, Including Optogenetics

Tuesday, May 10, 2016
Room 324-326
16:00 - 18:00
Moderators: Cornelius Faber, Yihong Yang

Deciphering the Functional Role of Locus Coeruleus-derived Norepinephrine using Chemogenetic fMRI and 18FDG-PET - Permission Withheld
Esteban Adrian Oyarzabal1,2, Manasmita Das3, Sung-Ho Adrian Lee4, Natale Sciolino2, Irina Evsyukova2, Patricia Jensen2, and Yen-Yu (Ian) Shih3
1Neurology, UNC-Chapel Hill, Carrboro, NC, United States, 2Laboratory of Neurobiology, NIEHS/NIH, Research Triangle Park, NC, United States, 3Neurology, UNC-Chapel Hill, Chapel Hill, NC, United States, 4UNC-Chapel Hill, Chapel Hill, NC, United States
This study examines how selective chemogenetic stimulation of noradrenergic neurons of the Locus Coeruleus (LC) in mice modulates cerebral metabolism and vascular tone. This was achieved by using a transgenic mouse line selectively expresses Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) in the LC noradrenergic neurons. A multimodal imaging approach was used, with MRI being used to evaluate hemodynamic changes and PET being used to assess glucose metabolism.  

Light-driven single-vessel fMRI on the rat hippocampus
Xuming Chen1,2, Hellmut Merkle1, and Xin Yu1
1High-Field Magnetic Resonance, Max Planck Institute for Biological Cybernetics, Tübingen, Germany, 2Neurology, Renmin Hospital of Wuhan University, Wuhan, China, People's Republic of
Previously, we have developed a single-vessel fMRI method to visualize the hemodynamic signal propagation from individual venules and arterioles in the deep layer cortex. Here, we combined single-vessel fMRI with optogenetic photo-activation to map vessel-specific fMRI signal from the rat hippocampus. A MGE sequence was used to distinguish the individual arterioles and venules penetrating the main structure of the hippocampus. The BOLD-fMRI signal was mapped to overlap with the individual venules. This result makes it possible to study the coupled neuronal and vascular interaction in the focal hippocampal stroke rat model, which may mimic the pathophysiological basis of transient global amnesia in human.   

Combined auditory and optogenetic fMRI for investigation of visual cortical descending modulation of auditory midbrain processing
Patrick P. Gao1,2, Russell W. Chan1,2, Alex T.L. Leong1,2, Celia M. Dong1,2, and Ed X. Wu1,2
1Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Hong Kong, China, People's Republic of, 2Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong, China, People's Republic of
In the auditory system, the midbrain inferior colliculus (IC) receives massive corticofugal projections, yet their functional implications remain unclear. Previous studies utilizing single neuron recordings and electrical activation or cryogenical inactivation of the cortex could not provide a cell-type specific understanding of the large-scale corticofugal modulation effects. This study combines auditory and optogenetic fMRI to investigate the corticofugal influences on auditory midbrain processing. Large-view fMRI was used to monitor the IC noise response during cell-type specific optogenetic stimulation of the VC. The results demonstrate the feasibility of this novel approach and show that VC normally facilitates auditory midbrain responses. 

Optogenetic fMRI reveals differences between paralemniscal and lemniscal somatosensory thalamocortical circuit
Alex T. L. Leong1,2, Russell W. Chan1,2, Patrick P. Gao1, Yilong Liu1,2, Xunda Wang1,2, Kevin K. Tsia2, and Ed X. Wu1,2
1Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Hong Kong, China, People's Republic of, 2Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong, China, People's Republic of
Identifying key differences between the paralemniscal and lemniscal pathway in the somatosensory system remains a challenge for electrophysiological studies due to limitations in spatial coverage. The use of optogenetic fMRI (ofMRI) however, provides an opportunity to map the large scale differences between the two pathways. Our key findings include, (1) differences in multisensory and motor system interaction when stimulating paralemniscal compared to lemniscal pathway and (2) differences in activity patterns when stimulating paralemniscal pathway within the whisking frequency range. In all, ofMRI provides an added dimension to existing electrophysiological studies to advance our understanding of information processing in thalamocortical circuits.  

Pharmacological MRI combined with DREADD-technology enables detection of induced brain activity in projections relevant for feeding behavior
Tessa J.M. Roelofs1,2, Geralda A.F. van Tilborg1, Mieneke C.M. Luijendijk2, Roger A.H. Adan2, and Rick M. Dijkhuizen1
1Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences, University Medical Center Utrecht, Utrecht, Netherlands, 2Translational Neurosciences, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, Netherlands
With the aim to develop a novel MRI-based approach for detection of activation in neuronal networks associated with feeding behavior in a rat model, we evaluated the potential of pharmacological MRI (phMRI) to detect DREADD (Designer Receptor Exclusively Activated by Designer Drug)-evoked neuronal activity. BOLD phMRI was conducted under 1.5% isoflurane anesthesia at 9.4T. Pharmacological activation induced a significant BOLD response in DREADD-targeted areas, which was confirmed by cFos-based immunohistochemistry of neuronal activation. Our study shows that phMRI allows detection of specific DREADD-evoked neuronal activity, providing exciting opportunities to assess network activity in association with feeding-related behavioral phenotypes.

Deciphering the Functional Connectome of the External Globus Pallidus with Electrical and Optogenetic Deep Brain Stimulation-fMRI
Daniel Albaugh1, Nathalie Van Den Berge2, Andrew Salzwedel3, Wei Gao3, Garret Stuber4, and Yen-Yu Ian Shih5
1Curriculum in Neurobiology, UNC-Chapel Hill, Chapel Hill, NC, United States, 2University of Ghent, Ghent, Belgium, 3Cedars-Sinai Medical Center, Los Angeles, CA, United States, 4Psychiatry, UNC-Chapel Hill, Chapel Hill, NC, United States, 5Biomedical Research Imaging Center, UNC-Chapel Hill, Chapel Hill, NC, United States
In this study, we unraveled the circuit and network connectivity of the rodent external globus pallidus (GPe), both in the healthy animals and a parkinson's disease model. We also employed multiple stimulation types (electrical and optogenetic), as well as fMRI modalities (evoked-fMRI and functional connectivity analyses) to provide an exhaustive analysis of this dynamic brain nucleus.

Study of the Transfer Functions of Hippocampal Subfields during a Spatial Memory Task using High-Resolution fMRI
Xiaowei Zhuang1, Zhengshi Yang1, Tim Curran2, and Dietmar Cordes1,2
1Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, United States, 2Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, United States
In this abstract, the input/output transfer relationship in human hippocampal subfields (mainly CA1, CA3, and DG) was studied using fMRI during a spatial memory task with increments in the change of FOV in the stimuli. Whole brain activation was obtained for all lure v/s control contrasts. Mean activation t value for each hippocampal subregions (CA1, CA2&3 and CA4&DG) was extracted, averaged over all the subjects and plotted against FOV changes to compare with the existing models. K-means clustering was then applied. Data from one of the k-means clusters showed a pattern separation/completion curve similar to the animal model.

Visualizing adaptation of the central serotonin circuit in the living brain
Bechara J. Saab1, Joanes Grandjean2, Alberto Corcoba3, Martin C. Kahn4, Louise A. Upton4, Erich Seifritz1, Fritjof Helmchen5, Isabelle Mansuy1, Edward O. Mann4, and Markus Rudin2
1University of Zurich, Zurich, Switzerland, 2University and ETH Zurich, Zurich, Switzerland, 3EPFL, Lausanne, Switzerland, 4University of Oxford, Oxford, United Kingdom, 5University and ETH Zurich, Zuerich, Switzerland
Mouse functional MRI was used to investigate the effect of selective stimulation of serotonergic neurons of the dorsal raphe via channelorodopsin-mediated optical control. Electrophysiological recordings in the nucleus and in projection areas confirmed neuronal activity changes upon illumination with blue light. Acute pharmacological modulation with fluoxetine, a serotonin reuptake inhibitor, lead to increased CBV response upon 5HT release, while animal restraint prior to measurements lead to a reduction of the elicited response. This study demonstrates the feasibility to assess a neurotransmitter function non-invasively at a whole brain level and investigate alterations in mood-controlling systems.

Direct mapping of functional connectivity with a novel MR-compatible high resolution brain stimulation array
Sung-Ho Lee1, Hsin-Yu Lai1, Yu-Chieh Jill Kai1, You-Yin Chen2, and Yen-Yu Ian Shih1
1University of North Carolina at Chapel Hill, Chapel Hill, NC, United States, 2Department of Biomedical Engineering, University of National Yang Ming, Taipei, Taiwan
In this study, we aim to provide in vivo evidence of using this novel electrode array for selective deep brain stimulation (DBS) in rats with simultaneous fMRI readouts. This novel development opens up a new avenue to explore and validate functional connectivity in the brain with a resolution and specificity that cannot be achieved by traditional fMRI or fcMRI approach.

Line scanning BOLD fMRI upon optogenetic stimulation - Permission Withheld
Franziska Albers1, Florian Schmid1, Lydia Wachsmuth1, and Cornelius Faber1
1Department of Clinical Radiology, University of Münster, Münster, Germany
With the line scanning technique BOLD responses can be recorded with 50 ms temporal resolution. Here line scanning fMRI was combined with optogenetic stimulation of excitatory neurons in rat somatosensory cortex. The light for optogenetic stimulation was delivered by an optical fiber implanted in the brain. It was possible to compare BOLD responses upon optogenetic and sensory stimulation with high temporal resolution and shorter times to reach half maximum were found for optogenetic stimulation. Furthermore the spatial resolution offered the possibility to observe cortical layer-specific BOLD signals.

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