Whole-brain mapping of effective connectivity by fMRI with cortex-wide patterned optogenetics

Functional magnetic resonance imaging (fMRI) with optogenetic neural manipulation is a powerful tool that enables brain-wide mapping of effective functional networks. To achieve flexible manipulation of neural exci-tation throughout the mouse cortex, we incorporated spatiotemporal programmable optogenetic stimuli generated by a digital micromirror device into an MRI scanner via an optical fiber bundle. This approach offered versatility in space and time in planning the photostimulation pattern, combined with in situ optical imaging and cell-type-specific or circuit-specific genetic targeting in individual mice. Brain-wide effective connectivity obtained by fMRI with optogenetic stimulation of atlas-based cortical regions is generally congruent with anatomically defined axonal tracing data but is affected by the types of anesthetics that act selectively on specific connections. fMRI combined with flexible optogenetics opens a new path to inves-tigate dynamic changes in functional brain states in the same animal through high-throughput brain-wide effective connectivity mapping.

Automated summary

Functional magnetic resonance imaging (fMRI) combined with optogenetic neural manipulation is a powerful tool for mapping brain-wide effective functional networks. By incorporating programmable optogenetic stimuli generated by a digital micromirror device into an MRI scanner, researchers can flexibly manipulate neural excitation in the mouse cortex. This approach allows for spatial and temporal versatility in planning photostimulation patterns, along with optical imaging and specific genetic targeting. The use of fMRI with optogenetics enables high-throughput brain-wide effective connectivity mapping, allowing for investigation of dynamic changes in functional brain states in the same animal.