Using transgenic technologies, we pursue the study of how heritable and de novo genetic variation in transporter genes leads to risk for neurological disorders. These studies initiate from identification of transporter genetic variation in humans with a range of disorders. Over the past decades we have identified such variation in subjects with autonomic dysfunction, neuromuscular disorders, ADHD and bipolar disorder, and autism. In subsequent efforts, we have generated the first mouse model of serotonin signaling perturbation impacting autism risk, and to the the first model model of perturbed dopamine signaling in ADHD. Ongoing studies look to contribute both human and mouse model efforts to disorders with deficits in acetylcholine and glutamate signaling. To these studies, we bring our substantial know-how in synaptic biochemistry and anatomy as well as physiological and behavioral methods. Our goal is not to reproduce all of the facets of a given disorder in the model. Such an effort naively assumes that all facets of human physiology and behavior can be reproduced in a rodent model. Rather, we seek to understand how changes at a molecular, cellular and organismal level can emerge when synaptic transporters are not working well, leading to both new fundamental insights into potential gene networks and affording the development of novel medications that can manipulate these networks to benefit those afflicted with brain disorders. We also capitalize on a rich battery of transgenic mice (and worms) that carry specific alterations in brain signaling pathways allowing us to further dissect components of these networks, and to determine which components, where in the brain, and when in development, are effects levied to to perturb physiology and behavior.