Dissection of brain-wide resting-state and functional somatosensory circuits by fMRI with optogenetic silencing

Edited by Peter Strick, Department of Neurobiology, University of Pittsburgh Brain Institute, Pittsburgh, PA; received July 19, 2021; accepted December 1, 2021
January 18, 2022
119 (4) e2113313119


Functional MRI (fMRI) has led to tremendous advancements in brain science by allowing noninvasive mapping of functional regions in response to various stimuli and noninvasive mapping of resting-state functional connectivity. Both evoked and resting-state functional networks contain multiple brain regions that are hierarchically yet reciprocally connected. Therefore, it is critical to determine the relative contributions of different circuits to fMRI findings to better understand brain functions and resting-state connectivity. Here, we adopted local silencing with optogenetic stimulation to suppress downstream networks and successfully dissected fMRI responses at the circuit level. This fMRI approach opens an avenue for understanding brain-wide, population-based neural circuits, allowing investigations of functional reorganization caused by neuropathological modifications and learning in individual animals.


To further advance functional MRI (fMRI)–based brain science, it is critical to dissect fMRI activity at the circuit level. To achieve this goal, we combined brain-wide fMRI with neuronal silencing in well-defined regions. Since focal inactivation suppresses excitatory output to downstream pathways, intact input and suppressed output circuits can be separated. Highly specific cerebral blood volume–weighted fMRI was performed with optogenetic stimulation of local GABAergic neurons in mouse somatosensory regions. Brain-wide spontaneous somatosensory networks were found mostly in ipsilateral cortical and subcortical areas, which differed from the bilateral homotopic connections commonly observed in resting-state fMRI data. The evoked fMRI responses to somatosensory stimulation in regions of the somatosensory network were successfully dissected, allowing the relative contributions of spinothalamic (ST), thalamocortical (TC), corticothalamic (CT), corticocortical (CC) inputs, and local intracortical circuits to be determined. The ventral posterior thalamic nucleus receives ST inputs, while the posterior medial thalamic nucleus receives CT inputs from the primary somatosensory cortex (S1) with TC inputs. The secondary somatosensory cortex (S2) receives mostly direct CC inputs from S1 and a few TC inputs from the ventral posterolateral nucleus. The TC and CC input layers in cortical regions were identified by laminar-specific fMRI responses with a full width at half maximum of <150 µm. Long-range synaptic inputs in cortical areas were amplified approximately twofold by local intracortical circuits, which is consistent with electrophysiological recordings. Overall, whole-brain fMRI with optogenetic inactivation revealed brain-wide, population-based, long-range circuits, which could complement data typically collected in conventional microscopic functional circuit studies.

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Data Availability

All study data are included in the article and/or supporting information. The imaging data that support the findings are available at XNAT Central (https://central.xnat.org/data/projects/OS-fMRI).


This project was funded by the Institute for Basic Science in Korea (IBS-R015-D1) and the NIH in the United States (NIH IRP ZIAMH002959). We thank Joonyeol Lee, Kamil Uludag, and Andrew You for helpful discussions, and Hyun-Kyung Lim for confocal imaging of brain slices.

Supporting Information

Materials/Methods, Supplementary Text, Tables, Figures, and/or References

Appendix 01 (PDF)
Dataset S01 (XLSX)


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Published in

Go to Proceedings of the National Academy of Sciences
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Proceedings of the National Academy of Sciences
Vol. 119 | No. 4
January 25, 2022
PubMed: 35042795


Data Availability

All study data are included in the article and/or supporting information. The imaging data that support the findings are available at XNAT Central (https://central.xnat.org/data/projects/OS-fMRI).

Submission history

Received: July 19, 2021
Accepted: December 1, 2021
Published online: January 18, 2022
Published in issue: January 25, 2022


  1. fMRI
  2. somatosensory network
  3. neuronal inhibition
  4. circuit dissection
  5. resting-state connectivity


This project was funded by the Institute for Basic Science in Korea (IBS-R015-D1) and the NIH in the United States (NIH IRP ZIAMH002959). We thank Joonyeol Lee, Kamil Uludag, and Andrew You for helpful discussions, and Hyun-Kyung Lim for confocal imaging of brain slices.


This article is a PNAS Direct Submission.



Won Beom Jung
Center for Neuroscience Imaging Research, Institute for Basic Science, Suwon 16419, Republic of Korea
Haiyan Jiang
Center for Neuroscience Imaging Research, Institute for Basic Science, Suwon 16419, Republic of Korea
Department of Biomedical Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
Unit on Functional Neural Circuits, NIH, Bethesda, MD 20892
Center for Neuroscience Imaging Research, Institute for Basic Science, Suwon 16419, Republic of Korea
Department of Biomedical Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea
Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, Suwon 16419, Republic of Korea


To whom correspondence may be addressed. Email: [email protected].
Author contributions: W.B.J. and S.-G.K. designed research; W.B.J. and H.J. performed research; W.B.J. analyzed data; W.B.J., S.L., and S.-G.K. wrote the paper; and S.L. provided critical discussion and insights.

Competing Interests

The authors declare no competing interest.

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    Dissection of brain-wide resting-state and functional somatosensory circuits by fMRI with optogenetic silencing
    Proceedings of the National Academy of Sciences
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