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. 2022 Oct 14;23(20):12268.
doi: 10.3390/ijms232012268.

Optogenetic fMRI for Brain-Wide Circuit Analysis of Sensory Processing

Jeong-Yun Lee  1 , Taeyi You  1   2   3 , Choong-Wan Woo  1   2   3 , Seong-Gi Kim  1   2   3
Affiliations

Optogenetic fMRI for Brain-Wide Circuit Analysis of Sensory Processing

Jeong-Yun Lee et al. Int J Mol Sci. .

Abstract

Sensory processing is a complex neurological process that receives, integrates, and responds to information from one's own body and environment, which is closely related to survival as well as neurological disorders. Brain-wide networks of sensory processing are difficult to investigate due to their dynamic regulation by multiple brain circuits. Optogenetics, a neuromodulation technique that uses light-sensitive proteins, can be combined with functional magnetic resonance imaging (ofMRI) to measure whole-brain activity. Since ofMRI has increasingly been used for investigating brain circuits underlying sensory processing for over a decade, we systematically reviewed recent ofMRI studies of sensory circuits and discussed the challenges of optogenetic fMRI in rodents.

Keywords: functional magnetic resonance imaging (fMRI); optogenetic fMRI (ofMRI); optogenetics; sensory processing; sensory system.

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Conflict of interest statement

The authors declare no competing interest.

Figures

Figure 2
Figure 2
Optogenetic strategies for fMRI. (A). Optogenetic stimulation of excitatory cell bodies (soma) or axon terminals. Orthodromic and antidromic propagation responding to the stimulating site (a). Postsynaptic activities by optogenetic stimulation (b). ofMRI response maps induced by optogenetic stimulation; fMRI response map by cell body stimulation of ACC and by axon terminal stimulation of ACC-PAG projection (c). (B). Optogenetic silencing by inhibitory opsins in excitatory pyramidal neurons (a) or excitatory opsins in inhibitory interneurons (b). ofMRI response of naïve and CFA-induced chronic pain model mice during ACC inhibition (c). (C). Combining optogenetics with sensory-evoked fMRI. fMRI with sensory stimuli (sensory-evoked fMRI) (a). Applying sensory-evoked fMRI to animal disease models (b) or conditioning behaviors (c). Silencing ofMRI combined with electrical stimulation (d). Adapted with permission from Lee et al. (2022) [20]. ACC; anterior cingulate cortex, PAG; periaqueductal gray.
Figure 1
Figure 1
Basics of optogenetics relevant to fMRI. (A) Light-sensitive opsins. Channelrhodopsin2 (ChR2; nonspecific cation channel), a representative excitatory opsin, which causes membrane depolarization (a). Inhibitory opsins such as halorhodopsin (NpHR; inward chloride pump) and archaerhodopsin (Arch; outward proton pump), which cause membrane hyperpolarization (b). (B–D) Three different approaches for the expression of light-sensitive opsins. (B) Transgenic mice with opsins in cell-type specific neurons. Transgenic Thy1-ChR2 mice for optogenetic excitation of pyramidal neurons. Transgenic VGAT-ChR2 mice for optogenetic inhibition of pyramidal neurons. (C) Virus-mediated expression of opsins for promotor-based gene delivery into neurons. Anterograde infection from cell bodies to axon terminals. Retrograde infection from axon terminals to cell bodies. (D) Cre-lox system for site- and cell-specific optogenetics. Diagram of the double-floxed inverse orientation (DIO) transgenic system.
Figure 3
Figure 3
Brain-wide optogenetic fMRI in sensory processing. (A). Schematic representation of sensory processing. (B). A summary of ofMRI papers, with reference in brackets [10,11,15,17,19,20,34,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64], related to sensory processing.
See this image and copyright information in PMC

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