Manipulating the activity of identified neurons in brain circuits is essential for studying how they are organized and how they produce behavior. Manipulating circuit activity can also be used to treat neurological and psychiatric diseases including Parkinson's Disease, depression and epilepsy. Optogenetic tools have revolutionized our ability to manipulate neuronal activity. We propose to create a set of complementary thermogenetic tools. These have the potential to reliably provide stronger levels of activation and may be activated with less invasive stimulus delivery systems. At present, such tools are used exclusively in flies. We propose to modify these tools to optimize them for use in mammalian systems. PUBLIC HEALTH RELEVANCE: Manipulating the activity of identified neurons in brain circuits is essential for studying how they are organized and how they produce behavior. Manipulating circuit activity can also be used to treat neurological and psychiatric diseases including Parkinson's Disease, depression and epilepsy. We propose to create a set of "thermogenetic" tools, for use in the mammalian brain, in which warmth-activated ion channels are used to conditionally activate defined subsets of neurons deep within the brain. The introduction of these tools will facilitate the investigation of brain circuit function in intact animals and open the possibility of a new set of tools for non-invasive stimulation of deep brain structures for therapeutic applications in humans.