Assistant Professor of Biology and Biological Engineering, Heritage Principal Investigator CALTECH, Pasadena, CA
Abstract: Our research group at Caltech employs optogenetics, chemogenetics, tissue clearing, and viral vectors to gain new insights on circuits underlying locomotion, reward, and sleep. In particular we will discuss how bidirectional manipulation of mesopontine cholinergic cell bodies exerted opposing effects on locomotor behavior and reinforcement learning and how these effects were separable via limiting photostimulation to PPN cholinergic terminals in the ventral substantia nigra pars compacta or to the ventral tegmental area, respectively (Xiao et al, Neuron, 2016). In addition to control of neuronal activity we need feedback on how exactly the tissue is responding to modulation. We have worked on two related topics: optical voltage sensors and imaging of single molecule RNA in cleared tissue. My group used directed evolution of opsins to make them better at reporting action potentials (Flytzanis et al, Nature Communications, 2014). Changes in RNA transcripts can also report on activity history of brain circuits. Preserving spatial relationships while accessing the transcriptome of selected cells is a crucial feature for advancing many biological areas, from developmental biology to neuroscience. Collaborators and us recently reported on methods for multi-color, multi-RNA, imaging in deep tissues. By using single-molecule hybridization chain reaction (smHCR), PACT tissue hydrogel embedding and clearing and light-sheet microscopy we detected single-molecule mRNAs in ~mm-thick brain tissue samples (Shah et al, Development, 2016) and by rRNA labeling we mapped the identity and growth rate of pathogens in clinical samples (DePas et al, mBio, 2016). Together these technologies can enable high content anatomical and functional mapping to define changes that affect cell function and health body-wide.