Next-generation brain imaging in freely moving animals

Calcium imaging in freely behaving animals allows for the tracking of neuronal activity under approximately normal behavioral conditions. However, the slow response time of calcium imaging inhibits high resolution voltage and temporal measurements. To address this issue, modern molecular tools have been developed to optically report the high-speed dynamics of neurons more accurately. Although imaging technologies for freely behaving animals are designed to capture the slower dynamics of calcium imaging with a frame rate of ≤ 30 Hz, they are incapable of tracking the faster dynamics of cutting-edge molecular reporters. In my postdoctoral work I will develop next generation imaging technologies for high-speed tracking of neural activity in freely behaving mice. To demonstrate the utility of this technology, I will monitor the behavior of genetically distinct neurons in the basal ganglia. Research in the Schnitzer lab using calcium imaging has called into question long-standing theories regarding its function. However, further progress in unraveling the mysteries of the basal ganglia have been limited by the slow and blurred response times of calcium imaging. The next generation imaging technology proposed in this work aims to reveal, for the first time, the exact activation patterns of genetically identified neurons in the basal ganglia which will ultimately provide further insight into its function. Answering these fundamental questions will allow us to better understand how these functions go awry during the development of diseases in the basal ganglia, such as Parkinson’s disease.