Functional circuit mapping of the anxious state: from optogenetics to CLARITY and eTANGO Sung-Yon Kim, SCSB Postdoctoral Fellow, Kwanghun Chung Laboratory, Picower Institute for Learning and Memory, MIT
Mammalian brains are staggeringly complex, with many billions of neurons forming an intricate neural network. A key question in neuroscience is how this neural network produces functional outcomes, such as cognition, emotion and bodily responses. To tackle this question, recent functional circuit mapping approaches attempt to map the entire anatomical connectivity (‘connectome’) and to identify the function of each neural circuit element (‘functional connectome’). Recent breakthroughs in neuro-technologies, such as optogenetics and CLARITY, are increasingly enabling these challenging investigations. In the first part of my talk, I will illustrate how optogenetics can be used to dissect the anxiety circuitry in the extended amygdala. We identified a surprising new role for the bed nucleus of the stria terminalis (BNST) in the coordinated modulation of diverse anxiety features, and clarified the underlying circuit mechanisms for selection of features for the assembly of the anxious state. In the second part, I will discuss the promises and challenges of the CLARITY technique and introduce a novel technique (termed eTANGO) that we have developed to achieve rapid and quantitative molecular phenotyping of intact tissues. By combining cutting-edge systems neuroscience tools, it would be possible to comprehensively understand the neural circuitry underlying various emotional states, such as anxiety, fear, reward and stress, at all structural, molecular and functional levels.