Research Departments & Organizations
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 activity relevant to weight regulation and 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.
Specialized Terms: Addictions; Animal Behavior; Ethology; Animal Nutrition; Diseases and Disorders; Drug Abuse; Eating Disorders; Etiology; Evolution; Genetic Manipulation; Natural History; Obesity; Psychiatry
Extensive Research Description
Broadly, our research seeks to define the molecular and neural basis of behavior. Most of the work focussed on neurocircuitry underlying responses to natural rewards (i.e. food) as well as drugs of abuse. We investigate the regulation and integration of these circuits with the longer term goal of understanding their relevance in disease, as well as the role that these circuits played in evolution. 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. Similar circuits likely underlie our motivation for physical activity, including exercise. Understanding the motivational systems that control feeding and activity 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.
Our experiments and progress depend upon our ability to effectively manipulate genes and neurons within the adult brain neurons. We are active in developing 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. We also apply optogenetic approaches for direct analysis of neural and neural circuit function. Current work aims to extend these approaches to manipulations of neural ensembles that are activated during specific behaviors.
Medial prefrontal D1 dopamine neurons control food intake.
Land BB, Narayanan NS, Liu RJ, Gianessi CA, Brayton CE, Grimaldi DM, Sarhan M, Guarnieri DJ, Deisseroth K, Aghajanian GK, DiLeone RJ. Medial prefrontal D1 dopamine neurons control food intake. Nature Neuroscience 2014, 17:248-53. 2014
Optogenetic inhibition of neurons by internal light production.
Land BB, Brayton CE, Furman KE, Lapalombara Z, Dileone RJ. Optogenetic inhibition of neurons by internal light production. Frontiers In Behavioral Neuroscience 2014, 8:108. 2014
Prefrontal D1 dopamine signaling is required for temporal control.
Narayanan NS, Land BB, Solder JE, Deisseroth K, DiLeone RJ. Prefrontal D1 dopamine signaling is required for temporal control. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109:20726-31. 2012
Gene profiling reveals a role for stress hormones in the molecular and behavioral response to food restriction.
Guarnieri DJ, Brayton CE, Richards SM, Maldonado-Aviles J, Trinko JR, Nelson J, Taylor JR, Gourley SL, DiLeone RJ. Gene profiling reveals a role for stress hormones in the molecular and behavioral response to food restriction. Biological Psychiatry 2012, 71:358-65. 2012
Regulation of nucleus accumbens activity by the hypothalamic neuropeptide melanin-concentrating hormone.
Sears RM, Liu RJ, Narayanan NS, Sharf R, Yeckel MF, Laubach M, Aghajanian GK, DiLeone RJ. Regulation of nucleus accumbens activity by the hypothalamic neuropeptide melanin-concentrating hormone. The Journal Of Neuroscience : The Official Journal Of The Society For Neuroscience 2010, 30:8263-73. 2010
Leptin receptor signaling in midbrain dopamine neurons regulates feeding.
Hommel JD, Trinko R, Sears RM, Georgescu D, Liu ZW, Gao XB, Thurmon JJ, Marinelli M, DiLeone RJ. Leptin receptor signaling in midbrain dopamine neurons regulates feeding. Neuron 2006, 51:801-10. 2006