English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Thesis

Mapping the local and brain-wide network effects by optogenetic activation with an MRI-guided robotic arm

MPS-Authors
/persons/resource/persons214924

Chen,  Y
Research Group Translational Neuroimaging and Neural Control, Max Planck Institute for Biological Cybernetics, Max Planck Society;
Max Planck Institute for Biological Cybernetics, Max Planck Society;

External Resource
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Chen, Y. (2020). Mapping the local and brain-wide network effects by optogenetic activation with an MRI-guided robotic arm. PhD Thesis, Eberhard-Karls-Universität, Tübingen, Germany.


Cite as: http://hdl.handle.net/21.11116/0000-0006-D939-6
Abstract
The optogenetically driven manipulation of circuit-specific activity has been very successful to enable functional causality studies in animals, but its global effect on the brain is rarely reported. Optical fiber-mediated optogenetic activation and neuronal Ca2+ recording in combination with fMRI provide a multi-modal fMRI platform with cross-scale brain dynamic mapping schemes, which can elucidate network activity upon circuit-specific optogenetic activation. However, despite highly promising prospects in animal brain research, there are still methodological and conceptual deficiencies, e.g., off-target effects and antidromic activity effects, which remain challenging for the current state of the art. To overcome these difficulties, this thesis describes two technical advances applied at the multi-modal fMRI platform, bridging the methodological and conceptual gap in optogenetics, brain function and animal behavior. First, an MRI-guided robotic arm (MgRA) is developed to increase the target accuracy for optogenetic manipulation or microinjection at the multi-modal fMRI platform, merging fMRI with concurrent deep brain optogenetics in rats. The 4-degrees-of-freedom MgRA allows high precision (50 μm per step) and sufficient mobility range (10 mm in the ventral-dorsal, rostral-caudal and medial-lateral directions) to manipulate fiber optic or injection needles into the brain in real time and provide high flexibility for multi-site targeting along the trajectory, which shows a clear advantage over the standard stereotaxic-based implantation strategy. Second, the multi-modal fMRI platform provides a specific calcium amplitude-based correlation analysis to study corpus callosum (CC)-mediated brain-wide network dynamics with taking antidromic activity effect into consideration. Since the callosal fibers are reciprocally projecting to two hemispheres, bilateral ortho-vs. antidromically evoked neural activity is difficult to disentangle. Here we not only detected strong antidromic activity, but also detailed temporal dynamics through CC-mediated orthodromic inhibitory activity. The calcium amplitude-based correlation map was created to reveal the brain-wide inhibitory effects from the CC-specific optogenetic stimulation. Last, this multi-modal fMRI platform was used to acquire the optogenetically driven neuronal Ca2+ with single-vessel BOLD and cerebral-blood-volume weighted signal from individual venules and arterioles, respectively, in the hippocampus. We characterized distinct spatiotemporal patterns of hippocampal hemodynamic responses that were correlated to the optogenetically evoked Ca2+ events and further demonstrated the significantly reduced neurovascular coupling (NVC) efficiency upon spreading depression-like Ca2+ events. These results provide a direct measure of the NVC function at varied hippocampal states in animal models. Overall, the technical advances described in this thesis demonstrate the powerful multi-modal fMRI platform to map, analyze and characterize the dynamic brain function across multiple scales and underscore the caution to interpret circuit-specific regulatory mechanisms underlying behavioral or functional outcomes with optogenetic tools.