To enable our core research program on understanding visual object representation, we are pursuing a number of projects focused on technology development, in the areas of ultrasonic neuromodulation, ultrasonic chemogenetics, and high-channel count electrophysiology.

 

Ultrasonic neuromodulation

In collaboration with Mikhail Shapiro, we have been working to develop ultrasonic neuromodulation as a means for focal, non-invasive perturbation of the human brain. We were very excited when we first read Jamie Tyler and colleagues’ 2010 Neuron paper reporting that low intensity transcranial pulsed ultrasound could elicit spikes in mouse motor cortex in vivo and evoke motor behaviors. To study the mechanisms of ultrasonic neuromodulation, we performed experiments combining sonication with wide field imaging in transgenic mice expressing GCAMP6 that had thinned skulls (Sato et al., 2018). We discovered that applying ultrasound to the brain leads to cortical activity patterns consistent with auditory pathway stimulation rather than direct neuromodulation. We’re currently conducting new experiments in genetically deaf mice to look for direct effects of neuromodulation in vivo without contamination by the large auditory side effect.

 

Ultrasonic chemogenetics

Mikhail Shapiro has recently developed a new method to non-invasively perturb large brain regions through acoustically targeted chemogenetics (Szablowski et al., 2018). In this method, the blood brain barrier is transiently opened using ultrasound to transduce neurons with virally-encoded engineered G-protein-coupled receptors. The cells expressing these receptors then respond to systemically administered bio-inert compounds by activation or inhibition. By spatially sculpting the ultrasound beam, any shape of receptor expression can be “painted.” We are working to adapt this technique for use in monkeys.

 

High-channel count electrophysiology 

We are working together with Michael Roukes and Ken Shepard to develop high channel count silicon probes for monkeys.