DESCRIPTION (provided by applicant): The mammalian brain, including the human brain, contains dozens of peptides that act as neurotransmitters between cells but whose function and modes of action are relatively unknown. This is particularly true in the basal ganglia in which the expression of peptides and of peptide receptors varies from cell to cell and nucleus to nucleus. The basal ganglia play a central role in controlling motor action selection - i.e. deciding what we do - and are at the heart of human disorders such as Parkinson's, Huntington's and drug addiction. We propose to study the function of peptides in the basal ganglia in order to understand how they signal and control the circuitry of this structure. We will make use of new technology developed in the laboratory that allows us to precisely release peptides in mammalian brain tissue using pulses of light. This will be used to analyze peptide function in tissue in which specific classes of neurons are marked or placed under optogenetic control. The proposed work will shed light on the basic biology of this conserved signaling system and will inform how its perturbation contributes to disease.

PUBLIC HEALTH RELEVANCE: Brain cells communicate via the release of short proteins - peptides - that can modulate the state of each cell. How peptides act is relatively unknown but their perturbation has been associated with human disease. We will use novel tools to understand the targets of peptide signaling and the mechanisms by which they control neural function.