Ralph Joseph DiLeone PhD

Associate Professor of Psychiatry and of Neurobiology

Research Interests

Addictions; Animal Behavior; Ethology; Animal Nutrition; Diseases and Disorders; Drug Abuse; Eating Disorders; Etiology; Evolution; Genetic Manipulation; Natural History; Obesity; Psychiatry

Research Summary

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 eating disorders.

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.

Selected Publications

  • Naryanan, N.S., Land, B.B., Solder, J.E., Deisseroth, K., and R.J. DiLeone (2012) Prefrontal D1 dopamine signaling is required for temporal control. Proceedings of the National Academy of Sciences, 109(50) 20726-31.
  • Guarnieri, D.J., et al., (2011) Gene profiling reveals a role for stress hormones in the molecular and behavioral response to food restriction. Biological Psychiatry, Published online, August 17th, 2011.
  • Sears, R.M., et al, (2010) Regulation of nucleus accumbens activity by the hypothalamic neuropeptide melanin-concentrating hormone. J. Neurosci. 30(24): 8263-8273.
  • Sharf, R. et al., (2010). Orexin signaling via the orexin 1 receptor mediates operant responding for food reinforcement. Biol. Psychiatry 67(8): 753-760.
  • Hommel, J.D., et al. (2006). Leptin receptor signaling in midbrain dopamine neurons regulates feeding. Neuron 51(6):801-810.

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