Delayed layer-specific CBV fMRI response is driven by somatostatin neuron-astrocyte-vasodilation pathway

Motivation: In human cognitive neuroimaging, layer-dependent CBV fMRI has increasingly been used to investigate neural circuits. A key question remains: what is the biological source of fMRI specificity at the laminar level? Goal(s): To evaluate the role of inhibitory somatostatin interneurons (SST) to hemodynamic responses and layer-specific CBV fMRI of forepaw stimulation. Approach: In this study, we used a multi-disciplinary approach that includes wide-field intrinsic optical imaging, calcium imaging, and layer-dependent fMRI with chemo-genetic or pharmacological interventions Results: Our findings suggest that SST interneuron activity is a crucial factor for the late, specific CBV-fMRI responses mediated by astrocytes. Impact: Our findings have significant implications for the neurovascular coupling field by revealing a novel contribution of interneurons and astrocytes. They also offer important insights for human fMRI, the interpretation of laminar-specific fMRI data and the design of laminar-specific fMRI paradigms.