Abstract
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.
Highlights
Functional MRI has led to tremendous advances in brain science by enabling noninvasive mapping of both functional regions with various stimuli and resting-state functional connectivity
The suppression of neural activity was confirmed by recording multiunit activities (MUAs) with 16-channel optoelectrode under the same photostimulation conditions used for Functional MRI (fMRI) studies
Based on fMRI data acquired after M1 or S2 silencing, we found that CC projections from M1 and S2 to the S1FL were negligible during FP stimulation
Summary
Functional MRI (fMRI) has led to tremendous advances in brain science by enabling noninvasive mapping of both functional regions with various stimuli and resting-state functional connectivity. Evoked fMRI can be used to detect the strength of hemodynamic responses to external stimuli [1,2,3], whereas resting-state fMRI (rs-fMRI) measures the degree of synchrony between fMRI time series among anatomically distinct brain regions at rest [4,5,6,7] Both evoked and resting-state functional networks contain multiple brain regions that are hierarchically yet reciprocally connected by ascending thalamocortical (TC), descending corticothalamic (CT), corticocortical (CC), and intracortical (IC) circuits [8]. 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. We examined how different cortical areas, including the primary somatosensory forelimb (S1FL), M1, and S2, affect activity in cortical and subcortical brain regions to determine causal relationships in the information flow among multiple brain areas
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