Acoustically Targeted Chemogenetics for Noninvasive Control of Neural Circuits

Existing treatments for brain disorders aim to modulate the activity of neural circuits, but are either not cell type-specific, lack spatial targeting, or require invasive procedures. Previously, we introduced an approach to modulating neural circuits noninvasively with spatial, cell-type, and temporal specificity called acoustically targeted chemogenetics, or ATAC. We use ultrasound to open the blood brain barrier to transduce neurons at specific locations in the brain with virally-encoded chemogenetic receptors. To show neuronal inhibition expressed inhibitory DREADD (hM4Di) throughout the hippocampus and tested mice in a fear conditioning protocol. The context fear test showed that mice treated with saline froze significantly more than those who had received CNO (p<2E-5, n=7,11) during the training phase.