We are interested in the function of neuromodulators. The nervous system uses two modes of chemical signaling at synapses. Fast signaling occurs by the release of small molecule neurotransmitters that activate ligand-gated ion channels. Slower signaling occurs by the release of neuromodulators that activate seven-transmembrane receptors coupled to heterotrimeric G proteins. Neuromodulators are typically neuropeptides, or monoamines such as dopamine, noradrenaline, and serotonin. Defects in neuromodulatory pathways do not usually lead to death, but can cause mental disorders such as depression, schizophrenia, autism, and attention deficit and hyperactivity disorder, as well as eating disorders and drug addiction. Neuromodulators are released from dense-core vesicles. Thus, a molecular understanding of neuromodulation requires both an understanding of the regulation of dense-core vesicle release as well as the G protein signal transduction pathways that respond to neuromodulatory signals.