Dissociation Between Hemodynamic and Metabolic Responses to Chemogenetic Modulation of Astrocytes in Mouse Visual...

Astrocytes play a critical role in brain homeostasis and energetics, yet their exact contribution to neurovascular and neurometabolic coupling is not fully elucidated. In particular, how astrocytic activity participates in shaping the functional neuroimaging signals relying on these processes remains unclear. In this study, we used chemogenetic modulation of astrocytes in the primary visual cortex, by activation of Gq-coupled designer receptors exclusively activated by designer drugs (DREADDs), to investigate their influence on spontaneous or sensory-driven hemodynamic fluctuations using functional ultrasound imaging (fUSi), as well as glucose uptake using [¹⁸F]FDG-positron emission tomography (PET). We found that astrocytic Gq-DREADD activation using clozapine-N-oxide (CNO) locally increased the amplitude of functional hyperemia during visual stimulation and vasomotion during resting-state. [¹⁸F]FDG signal was not significantly impacted, but changes in radiotracer uptake negatively correlated to changes in functional hyperemia across DREADDs-expressing mice. Our findings confirm that astrocytes are important players of sensory-driven as well as spontaneous cerebral hemodynamics, and nuance the view that astrocytic activity is the primary contributor of [¹⁸F]FDG PET. Moreover, they highlight astrocytes as a source of discrepancy between neurovascular and neurometabolic signals, both classically interpreted in terms of neuronal activity.