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

Abstract

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 excitation throughout the mouse cortex, we incorporated spatiotemporal programmable optogenetic stimuli generated by a digital micromirror device into an MR scanner via an optical fiber bundle for the first time. This approach offered versatility in space and time in planning the photostimulation pattern, combined with in situ optical imaging and cell-type 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 investigate dynamic changes in functional brain states in the same animal through high-throughput brain-wide effective connectivity mapping.

WITHDRAWN: Visual information is broadcast among cortical areas in discrete channels

“…All data are from mice unless otherwise specified in the figure . tural connectivity are available at the microscopic scale, but only one of the two is available for mesoscale and macroscale networks (Figure 7). Functional connectivity has been measured at the macroscale in mice using one-photon techniques (Ren and Komiyama, 2021) and fMRI (Kim et al, 2023), but these approaches lack cellular resolution, and the analyses to date do not provide a quantitative measurement of dispersion that can map onto the same axis, thus they are omitted from this discussion. Still, we can provide a large range of dispersion measurements (Figure 7).…”

No replication of direct neuronal activity–related (DIANA) fMRI in anesthetized mice

“…1A). For anesthesia, a mixture of ketamine and xylazine was initially injected intraperitoneally and was continuously infused intravenously ( 12 , 13 ) to maintain stable animal physiology. Toi et al ( 10 ) used the intraperitoneal delivery of supplementary anesthetics when needed ( 14 ), which results in well-known modulation of anesthetic depth during experiments ( 14 , 16 ).…”

“…All MRI experiments were performed under anesthesia in accordance with the guidelines of the Animal Welfare Act and the National Institutes of Health Guide for the Care and Use of Laboratory Animals. For anesthesia, a mixture of ketamine and xylazine (100 and 10 mg/kg, respectively) was initially injected intraperitoneally, and a dose of ketamine (45 mg/kg per hour) and xylazine (2.25 mg/kg per hour) was continuously infused intravenously ( 12 , 13 , 26 ). Note that Toi et al ( 10 ) used the supplementary bolus intraperitoneal delivery of ketamine (25 mg/kg) and xylazine (1.25 mg/kg) when needed ( 9 , 14 , 15 , 27 , 28 ), which induces anesthetic depth deep right after the bolus injection and a slow recovery to wakefulness ( 14 , 16 ).…”

“…Thus, we repeated the reported whisker stimulation experiments in virtually the same mouse model used by Toi et al ( 10 ). Compared to the original study, two improvements were made: (i) continuous infusion of anesthetics ( 12 , 13 ) rather than intermittent bolus injection of anesthetics ( 9 , 14 ) for maintaining stable animal physiology during fMRI studies and (ii) the use of 15.2 T rather than 9.4 T for enhancing SNR ( 15 ). All other parameters were the same as in the study by Toi et al ( 10 ).…”

Optogenetic fMRI reveals therapeutic circuits of subthalamic nucleus deep brain stimulation

“…We used optogenetics to confine the effects of DBS to local STN cell body activation 14,34 and leveraged brain-wide fMRI to map the modulated territories 26,30,[35][36][37][38][39][40][41][42][43][44][45][46][47][48] . Optogenetic stimulation modulated the BOLD signal in three major downstream brain areas: SNr, GP and CPu.…”