It is known that metabolism is precisely tuned to a dynamically stable state – a process often referred to as homeostasis, which allows organisms to survive and function effectively in a broad range of environmental conditions. To achieve this balanced state, the brain receives feedback signals from the body communicating metabolic status, integrates them with input from the external world as well as the emotional state, and then “appropriately” modifies feeding behaviors and physiological processes. When these regulatory functions go awry, eating disorders, obesity, cancer, or neurodegenerative diseases can result.
Figure 1. Hypothalamic neurons were identified under a 2-photon laser scanning microscope (2PLSM). Whole-cell patch clamp was achieved on a GFP-positive neuron. Red-fluorescent dye Alex 594 is included in the internal buffer of the glass pipette and allows the visualization of the neuronal structure.
The long-term goal of our laboratory is thus to bridge molecular, cellular, and system approaches to decipher the neuronal modulatory and circuitry mechanisms behind these processes. By leveraging and combining a battery of cutting-edge technologies, ranging from genetically engineered mouse models, recombinant viral vectors and viral tracing system, optogenetic and pharmacogenetic approaches, patch-clamp electrophysiology, to 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 feeding behaviors and metabolic regulations, 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 molecules, ion channels, or cellular signaling pathways are rooted to bear these physiological processes and how their dysfunctions contribute to the pathogenesis of disorders in both metabolism and cognition. Understanding these above questions will provide novel insights on the treatment and prevention of various health-threatening human diseases.