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

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.

Novel inductively-coupled ear-bars (ICEs) for fMRI signal enhancement in rat entorhinal cortex

“…S5 , details in Methods), the DMN is presented in Fig.4d , including prelimbic cortex, cingulate cortex, auditory cortex, posterior parietal cortex, and retrosplenial cortex. These results provide strong evidence for highly reliable detection of BOLD fMRI signals under experimental conditions, which are highly consistent with reports from other researchers [37-42].…”

Frontal Cortex Gates Distractor Stimulus Encoding in Sensory Cortex

“…Additionally, this framework provides little motivation for studying the impacts of top-down regions on pre-stimulus activity. However, we casually demonstrated that wMC robustly modulates S1 before stimulus onset in both anesthetized and awake behaving animals (see also Jung et al, 2022). Importantly, this pre-stimulus modulation is context-dependent, with a stronger drive onto putative inhibitory neurons in distractor-aligned S1.…”

“…Additionally, S1 receives top-down inputs from ipsilateral frontal cortex, most robustly from the whisker region of motor cortex (wMC). Stimulation and suppression studies have demonstrated robust yet varied impacts of wMC activity on S1, including through excitation (Jung et al, 2022; Lee et al, 2008; Manita et al, 2015; Petreanu et al, 2012; Rocco & Brumberg, 2007; Xu et al, 2012; Zagha et al, 2013), inhibition (Kinnischtzke et al, 2014; Zagha et al, 2016), and dis-inhibition (Lee et al, 2013). The impacts of wMC on S1 in the context of distractor suppression is unknown.…”

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

“…Conventional FC measured by fMRI relies on covaried hemodynamic modulations at a resting state (RS). However, the underlying sources of RS FC are unclear and do not faithfully reflect neuronal RS circuits in mice 47 . Thus, we adopted EC measurements by directly modulating neuronal activities in source regions and reading out corresponding responses in the entire brain by fMRI.…”