Fiber-optic implant for simultaneous fluorescence-based calcium recordings and BOLD fMRI in mice.
Felix SchlegelYaroslav SychAileen SchroeterJillian L StobartBruno WeberFritjof HelmchenMarkus RudinPublished in: Nature protocols (2018)
Despite the growing popularity of blood oxygen level-dependent (BOLD) functional MRI (fMRI), understanding of its underlying principles is still limited. This protocol describes a technique for simultaneous measurement of neural activity using fluorescent calcium indicators together with the corresponding hemodynamic BOLD fMRI response in the mouse brain. Our early work using small-molecule fluorophores in rats gave encouraging results but was limited to acute measurements using synthetic dyes. Our latest procedure combines fMRI with optical detection of cell-type-specific virally delivered GCaMP6, a genetically encoded calcium indicator (GECI). GCaMP6 fluorescence, which increases upon calcium binding, is collected by a chronically implanted optical fiber, allowing longitudinal studies in mice. The chronic implant, placed horizontally on the skull, has an angulated tip that reflects light into the brain and is connected via fiber optics to a remote optical setup. The technique allows access to the neocortex and does not require adaptations of commercial MRI hardware. The hybrid approach permits fiber-optic calcium recordings with simultaneous artifact-free BOLD fMRI with full brain coverage and 1-s temporal resolution using standard gradient-echo echo-planar imaging (GE-EPI) sequences. The method provides robust, cell-type-specific readouts to link neural activity to BOLD signals, as emonstrated for task-free ('resting-state') conditions and in response to hind-paw stimulation. These results highlight the power of fiber photometry combined with fMRI, which we aim to further advance in this protocol. The approach can be easily adapted to study other molecular processes using suitable fluorescent indicators.
Keyphrases
- resting state
- functional connectivity
- high resolution
- small molecule
- contrast enhanced
- single molecule
- diffusion weighted imaging
- randomized controlled trial
- magnetic resonance imaging
- high speed
- healthcare
- high fat diet induced
- quantum dots
- living cells
- soft tissue
- metabolic syndrome
- computed tomography
- liver failure
- optical coherence tomography
- intensive care unit
- label free
- high intensity
- diffusion weighted
- transcription factor
- insulin resistance
- brain injury
- dna binding
- aortic dissection
- skeletal muscle
- wild type