ABSTRACT Acoustic technologies such as optoacoustic (OA) imaging and ultrasound neuromodulation (USNM) are poised to revolutionize deep tissue, high-resolution, large-scale, in vivo imaging and neurostimulation in mammalian organisms. These advances are enabled by the high tissue penetrability of ultrasound (US) waves, and present untapped and exciting opportunities for accessing structures throughout the mammalian brain for precise control and measurement of neural activity. We have recently introduced hybrid tools for parallel OA imaging with GCaMP-type indicators and US neuromodulation in the cortex in vivo. Despite these advances, improvements in the spatial resolution, as well as the capability to make full use of the deep-tissue access afforded by these modalities, are highly desirable. We propose to undertake technological developments designed to optimize these methods for cellular resolution, deep-tissue functional imaging and neurostimulation, through both optimization of hardware and ‘wet-ware’, such as near-infrared (NIR) functional probes. These developments to optimize functional OA signals will enable imaging of neural activity at tissue depths that far exceed those accessible with optical techniques alone. The new framework will then be applied and tested in the mouse olfactory system, whose spatial-temporal scale of neural activity is well matched to that of the proposed technique, and which will significantly benefit from a combined imaging and perturbation strategy for linking large-scale odor-evoked neural activity in the olfactory bulb to mouse behavior.