PROJECT SUMMARY
The goal of this project is to understand the neurobiological underpinnings of the effects of ultrasound
(US) on neural activity. US can modify action potential activity in neurons in vitro and in vivo without damaging
neural tissue. This phenomenon can be applied in powerful new tools for basic and clinical neuroscience, with
broad impact on public health issues related to mental and neurological disorders. To guide use of this new
tool, our research will provide insight into the physical, biophysical and neural mechanisms underlying US
neuromodulation.
Our approach is unique in applying and integrating mechanistic studies of US neuromodulation at levels
of complexity ranging from the single cell to the whole animal. We aim to understand the relationship between
US 1) the physical processes that transform acoustic energy to effects on biological systems and the resulting
measurable physical variables (Aim 1), 2) the biophysical transduction processes together with the resulting
measurable biophysical effects (Aim 2) 3) the subsequent neural integration processes that lead to the final
output of the neural system or behavior (Aim 3). We will address these questions in experiments across three
model systems (the in vivo mouse model, in vitro salamander and mouse retina, and single hippocampal
pyramidal cells in acute and cultured brain slices), focusing on hypotheses guided by our results thus far.
US neuromodulation is likely to have significant impact on public health. Brain stimulation therapies are
used to treat Parkinson's disease, dystonia, and epilepsy and hold promise for many others. Compared to
current brain stimulation techniques that rely on invasive implanted electrodes or have limited spatial resolution
and depth penetration (e.g., transcranial magnetic stimulation), US offers an ideal combination of spatial
resolution, depth penetration, and non-invasiveness. US neuromodulation can also be implemented in
prosthetic devices; for example, to stimulate retinal circuitry to restore vision. In addition, US neuromodulation
promises to become an enormously useful research tool in basic neuroscience, and it is therefore relevant to
all mental and neurological disorders of public health concern. However, all these outcomes depend on the
ability to apply US neuromodulation with well-controlled, predictable results. Achieving this goal requires a
detailed mechanistic understanding of US neuromodulation that our multidisciplinary research project will
provide.