Neural Circuits of Interoception

Physiological theories of emotion have hypothesized that bodily signals such as accelerated heart rate can contribute or even give rise to changes in emotional states. To determine how the body communicates with the brain, we established a noninvasive optical pacemaker that enabled direct depolarization of cardiomyocytes in freely-moving mice. We find that optically-induced tachycardia accentuated anxiety-like behavior and that cardiac interoception was represented in the posterior insular cortex. Optogenetic inhibition of the insula, a region of the brain involved in both processing of viscerosensory signals and the regulation of emotions, attenuates cardiogenic effects on anxiety. These findings support a more generalized function for the insula in monitoring both consummatory and entirely internal interoceptive states to instruct relevant behavioral responses. 

Technology Development

Non-invasive optogenetics

Cell-type-specific, non-invasive control of the central and peripheral nervous system would greatly enhance our understanding of neurophysiology. We have demonstrated that the potent channelrhodopsin ChRmine can achieve transcranial photoactivation of defined neural circuits, including midbrain and brainstem structures, at depths of up to 7 mm with millisecond precision. By using systemic viral delivery of ChRmine, we were able to modulate behavior without surgery, enabling implant-free deep brain optogenetics. 

Nanoscale bioelectronic devices

Aberrant activity of electroactive cells underlies neurological disorders like epilepsy. Control of ionic current through cell membranes can restore balance to electrochemical signals, but many neuromodulation approaches are limited to invasive surgically-implanted devices. To achieve both minimally-invasive and cell-type-specific control, we have developed nanoscale devices for remote control of cellular function. For example, we have demonstrated that remote heating of magnetic nanoparticles is sufficient to activate neurons expressing heat-sensitive ion channels in mice—enabling the first example of minimally-invasive cell type specific control in the deep brain. We are interested in engineering nanoscale devices as actuators and sensors to interface with the nervous system in order to explore the limits of device miniaturization.

Hydrogel tissue chemistry

Imaging biomolecules and cells within their spatial context can provide insight into the function and dysfunction of complex biological systems. Over the past decade, chemical methods to transmute tissue into optically transparent substrates have enabled the mapping of features across multiple length scales (from individual mRNA strands to neural projections spanning the mouse brain) . We have previously identified a number of multifunctional epoxides (chemical resins commonly used in building and construction) that can stabilize biomolecules and tissue within transparent tissue. This method, called SHIELD, can be used for volumetric mapping of biomolecular features (mRNA, proteins, fluorescent reporters) within intact, fixed tissue.