Ralph Joseph DiLeone PhD
Associate Professor of Psychiatry and of Neurobiology
Addictions; Animal Behavior; Ethology; Animal Nutrition; Diseases and Disorders; Drug Abuse; Eating Disorders; Etiology; Evolution; Genetic Manipulation; Natural History; Obesity; Psychiatry
Our goal is to establish an understanding of the molecular and neuronal circuits that are responsible for controlling reward-related behavior. We seek to define brain mechanisms that regulate eating and are important in the development of obesity. Dysfunction of these appetitive behaviors also contributes to related pathological states, such as eating disorders, drug addiction, and depression. We are identifying critical molecules and neural circuitry that connect metabolic signals to behavioral output. Projects in the lab are aimed at better defining the molecular and neural mechanisms that integrate the hypothalamus and peripheral metabolic signals with brain regions that drive, and control, motivated behavior. In addition, the lab is active in developing tools that facilitate efforts to better understand the molecular and cellular basis of neural plasticity and animal behavior.
Extensive Research Description
Broadly, our research seeks to define the common elements and
differences between the molecular neurocircuitry underlying responses
to "natural" reward (i.e. food) versus that which mediates responses to
drugs of abuse and the development of addiction. We investigate the
regulation and integration of these circuits with the longer term goal
of understanding their relevance in both evolution and human disease.
It is notable that the motivation to ingest food, though highly
adaptive during most of our natural history, has proven to be
incompatible with the current state of excess food supply.
Understanding the motivational systems that control feeding will give
us insight into the molecular mechanisms of a complex behavior, and
will ultimately serve to better define the etiology of obesity and
While there have been identified important circulating factors, such as leptin, that convey nutritional and energy supply status to the brain, the mechanism by which this information is processed and integrated within the brain remains a mystery. Our data suggest a number of molecular links that connect traditional "feeding centers", such as the hypothalamus, to "reward centers," such as the mesolimbic dopamine systems.
Our experiments depend upon our ability to effectively manipulate gene function in adult brain neurons. We continue to develop viral and transgenic techniques for conditional genetic analysis of neural function and behavior, including the development of viral constructs that will allow for more systematic studies of gene function in the context of neural circuits.