When Photons Meet Protons: Optogenetics, Calcium Signal Detection, and fMRI in Small Animals
In the new era of brain research, highlighted by the Human Brain Project and BRAIN Initiative, how to link the cellular, circuit, and system aspects of brain function is one of the key aims of this mission. The multimodal neuroimaging methodology has prov
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Xin Yu
Contents 31.1
Overview
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31.2 ethodological Development M 31.2.1 O ptogenetics 31.2.2 G enetically Encoded Calcium Indicators (GECIs) 31.2.3 Small Animal fMRI
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31.3 ultimodal Applications M 31.3.1 O ptogenetic fMRI Studies 31.3.2 Simultaneous fMRI with Calcium Recording
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31.4
Future Studies
References
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31.1 Overview
form. Among the numerous efforts on brain functional mapping, the combination of optogenetics, calcium signal detection by genetically encoded indictors, and functional magnetic resonance imaging (fMRI) presents a unique perspective to better understand brain function. This chapter will focus on the recent application of optogenetic tools for fMRI studies, as well as a recent development of the fiber optic-mediated simultaneous calcium recording with fMRI. These studies lead to a new concept, the single unit of neurovascular coupling (SUNC) (Fig. 31.1), to better understand the signal propagation through the neuron-glia-vessel network in the brain of rodents.
31.2 Methodological Development 31.2.1 Optogenetics
In the new era of brain research, highlighted by the Human Brain Project and BRAIN Initiative, how to link the cellular, circuit, and system aspects of brain function is one of the key aims of this mission. The multimodal neuroimaging methodology has provided us a promising plat-
X. Yu Translational Neuroimaging and Neural Control Group, High Field Magnetic Resonance Department, Max Planck Institute for Biological Cybernetics, Tuebingen, Germany e-mail: [email protected]
31.2.1.1 L ighten the Brain with Channelrhodopsin The optogenetic studies, i.e., channelrhodopsin- mediated optical control of neural activity, can be traced back to the study on the phototactic responses of Chlamydomonas reinhardtii, a single- cell green alga (Schmidt and Eckert 1976). Calcium ions were reported to mediate the swimming direction of the alga (Schmidt and Eckert 1976), and the rhodopsin in the eyespot of the alga could regulate calcium current in response to flash of light (Harz and Hegemann
© Springer International Publishing AG 2017 F. Kiessling et al. (eds.), Small Animal Imaging, DOI 10.1007/978-3-319-42202-2_31
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Fig. 31.1 The “single unit” of neurovascular coupling is based on the fiber optic inserting into the targeted brain region of interests. The single-vessel fMRI method was previously developed by Yu et al. to specifically map fMRI signal from individual vessels penetrating the cortex of the rat brain (Yu et al. 2012, 2014). Both light-sensitive proteins (e.g., channelrhodopsin-2, ChR2) (Nagel et al. 2003) and genetically encoded calcium indicators (e.g., GCaMP6) (Akerboom et al. 2013) can be specifically expressed into neurons or glial cells. Upon optical stimulation, the calcium signal from distinct groups of cells can
be directly recorded by the fiber optic, and the fMRI signal from individual vessels (arterioles and venules) surrounding the fiber-optic
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