Ultrasonic neural control and neuroimaging in the awake, mobile, and behaving small rodent

To enable next-generation analyses of how neuropsychiatric drugs induce their physiologic and  behavioral effects, we need technologies that allow noninvasive application of a given drug to a target brain region, while recording the resultant changes in neural activity in the awake, behaving small animal, without invasive surgical or genetic interventions upon the brain. To enable noninvasive targeted pharmacologic neuromodulation, we have developed ultrasonic drug uncaging, in which ultrasound induces localized drug release from intravenously administered nanoparticles. Complementarily, functional ultrasound (fUS) imaging has been recently developed, in which ultrasound images neural activity via changes in microvascular perfusion, with much greater resolution than fMRI. Additionally, transducers have been described that enable fUS in the awake and mobile small rodent, although these transducers may induce motion limitations that could impede behavioral analysis. We propose to design a lightweight, wearable system for integrated ultrasonic drug uncaging and fUS neuroimaging to noninvasively pharmacologically modulate a brain target and then image the resultant changes in neural activity, while the small animal is awake and performing a behavioral task of interest, without significant motion limitations. This design would leverage our investigatory team’s pioneering efforts in ultrasonic drug uncaging, capacitive micromachined ultrasonic transducer design, and small-vessel Doppler imaging.