The lateral hypothalamus (LH) plays a substantial role in a number of functions including sensorimotor integration, energy homeostasis, sleep-wake regulation, addiction, emotion and regulation of the autonomic nervous system. It has been shown that the LH is a central hub receiving physiological, behavioral and environmental inputs from and sending outputs to other brain structures to participate in homeostatic and behavioral functions. Despite its critical role in the survival of individuals and species, it is largely unclear how the LH integrates information from internal and external environments to exert its actions. Moreover, it is also not clear how the neural circuitry centered on neurons in the LH make adaptive changes to accommodate physiological, behavioral and environmental changes. Our long-term goal is to understand the logic of how signaling at molecular, cellular and circuit levels leads to the emergence of instinctive behaviors critical for animal survival. By using transgenic mice expressing GFP exclusively in hypocretin- or melanin concentrating hormone (MCH)-containing neurons, we are allowed to directly observe activity in these neurons in vitro and examine changes in these neurons in vivo. By using mice with a deficiency in either the hypocretin or MCH system, we are starting to reveal the crosstalk between these two systems in behaviors such as food intake, sleep regulation and drug addiction. Specifically, the questions that we are pursuing include: 1) how neural circuitry in the LH participates in the regulation of homeostatic and behavioral functions of the brain; 2) how neural circuitry in the LH is modified by physiological, behavioral and environmental changes in mature animals; 3) how maternal and early postnatal experience leads to changes in the development of neural circuitry responsible for dysfunctions of the LH during adulthood. Currently we have made significant progress on understanding neuroplasticity in the LH area in energy homeostasis and sleep regulation. Although each brain region has its own specificity, all regions share many common features. The basic questions relating to the mechanisms underlying brain function bring neuroscientists in various fields together and form the basis for cooperation. In addition to our own independent research, with great pleasure and interest we are looking forward to working with and sharing with other scientists of various backgrounds in order to understand the mystery of the brain.