We request funding to establish a voltage-sensitive dye (VSD) imaging setup in the Department of Biology at Emory University. This setup will greatly enhance the research capability of the neuroscience faculty in the Department with active NIH funding (Drs. Jaeger, Calabrese, Liu and Prinz). The P.I. (Dr. Jaeger) has a long track record in the research of basal ganglia and cerebellar networks. To extend this analysis to the level of cortical activity modulation due to basal ganglia and cerebellar feedback loops would be innovative, impactful, and timely. VSD imaging of mouse cortical activity in vivo will be a crucial tool to determine the temporal and spatial effects of basal ganglia and cerebellar activation on cortical activity. Similarly, the research of Dr. Liu is concerned with cortical actiity patterns, albeit the activation following social ultrasound signaling in mice on auditory circuits. VSD imaging would allow this work to progress towards a better understanding of spatial and temporal signal flow beyond primary auditory cortex. For both Dr Jaeger and Dr. Liu this technology would be particularly timely to implement soon, as the development of optogenetic stimulation techniques and genetic voltage-sensitive indicators will allow us to address important questions with an expected high impact in novel findings. The work of Drs. Calabrese and Prinz explores the function of invertebrate pattern generation circuits in the leech heartbeat circuit and crab/lobster stomatogastric ganglion, respectively. However, similarly to the question of spatial dynamics of cortical dynamics, these ganglia consist of a spatial network in the respective ganglia with complex activity patterns that can be fruitfully surveyed by voltage-sensitive dye imaging techniques. The equipment we request will allow us to flexibly conduct experiments on the spatial scale required in rodents in vivo (10x10 mm area of interest) and invertebrate ganglia (1x1 mm area of interest) by mounting a state of the art dual CMOS camera system either on an in vivo imaging setup or on an Olympus BX50 microscope. Both setups will share manipulators and amplifiers for simultaneous electrophysiological recordings. A substantial amount of the basic equipment (Olympus BX50 microscope, vibration isolation table, recording amplifiers) needed for this setup will be contributed by the major investigators, and a dedicated room is made available by the Dept. of Biology. The core item requested is the dual camera CMOS system, along with the necessary optical equipment (beam splitter, software, etc), and auxiliary hardware. The expectation from obtaining this setup is that innovative and timely methods will be available to the established research programs of the major investigators, and allow the development of junior faculty as well. The health impact is also highly relevant, in that the research by the Jaeger lab is directly applied to establishing Parkinson's disease mechanisms, work in the Liu lab is relevant to the study of autism, and work in the Calabrese and Prinz labs demonstrate fundamental mechanisms of neuromodulation and homeostasis that underlie understanding of how pathological brain activity may arise as a maladaptation of normal dynamics.
