Abstract
Optical fiber-mediated optogenetic activation and neuronal Ca2+ recording in combination with fMRI provide a multi-modal fMRI platform. Here, we developed an MRI-guided robotic arm (MgRA) as a flexible positioning system with high precision to real-time assist optical fiber brain intervention for multi-modal animal fMRI. Besides the ex vivo precision evaluation, we present the highly reliable brain activity patterns in the projected basal forebrain regions upon MgRA-driven optogenetic stimulation in the lateral hypothalamus. Also, we show the step-wise optical fiber targeting thalamic nuclei and map the region-specific functional connectivity with whole-brain fMRI accompanied by simultaneous calcium recordings to specify its circuit-specificity. The MgRA also guides the real-time microinjection to specific deep brain nuclei, which is demonstrated by an Mn-enhanced MRI method. The MgRA represents a clear advantage over the standard stereotaxic-based fiber implantation and opens a broad avenue to investigate the circuit-specific functional brain mapping with the multi-modal fMRI platform.
Highlights
Optical fiber-mediated optogenetic activation and neuronal Ca2+ recording in combination with functional magnetic resonance imaging (fMRI) provide a multi-modal fMRI platform
Besides an ex vivo precision evaluation, we present a series of in vivo studies showing the whole brain activity patterns upon optogenetic stimulation of MRI-guided robotic arm (MgRA)-targeted nuclei in the lateral hypothalamus (LH) or thalamus in a step-wise manner and with simultaneous fiber-optic calcium recordings to specify the region-specific optogenetic activation patterns
Both MR compatible camera and surface transceiver coil are included for monitoring the fiber optic insertion inside the MR scanner. c Stepper motors implemented at the back part of the MgRA to control up to four degrees-of-freedom movement
Summary
Optical fiber-mediated optogenetic activation and neuronal Ca2+ recording in combination with fMRI provide a multi-modal fMRI platform. We developed an MRI-guided robotic arm (MgRA) as a flexible positioning system with high precision to real-time assist optical fiber brain intervention for multi-modal animal fMRI. Using MgRA assisted fiber-optic insertion in combination with real-time fMRI, we can provide a step-wise optogenetic activation scheme to allow multi-site targeting through a fiber insertion trajectory during the fMRI study This strategy can improve the precision, and provide a thorough view to examine the subtle differences in the whole brain activation patterns when targeting the subregions of the functional nuclei of interest. Besides an ex vivo precision evaluation, we present a series of in vivo studies showing the whole brain activity patterns upon optogenetic stimulation of MgRA-targeted nuclei in the LH or thalamus in a step-wise manner and with simultaneous fiber-optic calcium recordings to specify the region-specific optogenetic activation patterns. We demonstrate a series of high precision brain interventional applications in the context of multi-modal neuroimaging using the MgRA system
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