The long-term interest of our laboratory is to bridge molecular, cellular, and system approaches to decipher the neuronal modulatory and circuitry mechanisms underlying diabetes and obesity. By leveraging and combining a battery of cutting-edge technologies, including genetically engineered mouse models, recombinant viral vectors and viral tracing system, optogenetic and pharmacogenetic approaches, patch-clamp electrophysiology, 2-photon laser scanning microscopy, and 2-photon laser uncaging methods (2PLSM/2PLU), we are interrogating the following questions: 1) how neurons in the central nervous system translate their intrinsic firing properties to the controlling of energy and glucose homeostasis, and what circuits are involved; 2) how metabolic signals, including circulating metabolites, hormones, and neuropeptides, act on circuit neurons, shape their firing outputs, and modulate related synaptic neurotransmission; and 3) what kinds of receptors, ion channels, or cellular signaling molecules are rooted to bear these physiological processes and how their dysfunctions contribute to the pathogenesis of diabetes and the related complications. Understanding these above questions will provide novel insights on the treatment and prevention of diabetes.