Ralph DiLeone, PhD
Research & Publications
Biography
News
Locations
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 activity relevant to weight regulation and the development of obesity. We also study neural mechanisms underlying drug addiction including translational projects aimed at treatment. Moreover, we have an interest understanding the drive and motivation for physical activity as a relatively understudied but key component of body weight regulation.
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 focused 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 current translational studies on opioid use disorder are focused at evaluating specific therapeutics for their mechanisms as well as their efficacy in animal models of dependence and drug seeking.
Our experiments and progress depend upon our ability to effectively monitor and manipulate neurons within the adult brain. We are active in using viral and transgenic techniques for conditional genetic analysis of neural function and behavior. The lab also leverages conditional viral approaches to evaluate activity (via fiber photometry) or to manipulate (via optogenetics) specific circuits and neuronal types during behavior.
Coauthors
Research Interests
Feeding and Eating Disorders; Ethology; Neurobiology; Obesity; Psychiatry; Exercise; Substance Abuse Detection; Natural History; Glucose Metabolism Disorders; Animal Nutrition Sciences
Selected Publications
- Brain responses to nutrients are severely impaired and not reversed by weight loss in humans with obesity: a randomized crossover studyvan Galen K, Schrantee A, ter Horst K, la Fleur S, Booij J, Constable R, Schwartz G, DiLeone R, Serlie M. Brain responses to nutrients are severely impaired and not reversed by weight loss in humans with obesity: a randomized crossover study. Nature Metabolism 2023, 5: 1059-1072. PMID: 37308722, DOI: 10.1038/s42255-023-00816-9.
- Medial Nucleus Accumbens Projections to the Ventral Tegmental Area Control Food ConsumptionBond CW, Trinko R, Foscue E, Furman K, Groman SM, Taylor JR, DiLeone RJ. Medial Nucleus Accumbens Projections to the Ventral Tegmental Area Control Food Consumption. Journal Of Neuroscience 2020, 40: 4727-4738. PMID: 32354856, PMCID: PMC7294796, DOI: 10.1523/jneurosci.3054-18.2020.
- Medial prefrontal D1 dopamine neurons control food intakeLand BB, Narayanan NS, Liu RJ, Gianessi CA, Brayton CE, M Grimaldi D, Sarhan M, Guarnieri DJ, Deisseroth K, Aghajanian GK, DiLeone RJ. Medial prefrontal D1 dopamine neurons control food intake. Nature Neuroscience 2014, 17: 248-253. PMID: 24441680, PMCID: PMC3968853, DOI: 10.1038/nn.3625.
- Ketogenic diet enhances the effects of oxycodone in miceTrinko R, Diaz D, Foscue E, Thompson S, Taylor J, DiLeone R. Ketogenic diet enhances the effects of oxycodone in mice. Scientific Reports 2023, 13: 7507. PMID: 37160959, PMCID: PMC10170077, DOI: 10.1038/s41598-023-33458-8.
- Orbitofrontal Circuits Control Multiple Reinforcement-Learning ProcessesGroman SM, Keistler C, Keip AJ, Hammarlund E, DiLeone RJ, Pittenger C, Lee D, Taylor JR. Orbitofrontal Circuits Control Multiple Reinforcement-Learning Processes. Neuron 2019, 103: 734-746.e3. PMID: 31253468, PMCID: PMC6893860, DOI: 10.1016/j.neuron.2019.05.042.
- Optogenetic stimulation of medial prefrontal cortex Drd1 neurons produces rapid and long-lasting antidepressant effectsHare BD, Shinohara R, Liu RJ, Pothula S, DiLeone RJ, Duman RS. Optogenetic stimulation of medial prefrontal cortex Drd1 neurons produces rapid and long-lasting antidepressant effects. Nature Communications 2019, 10: 223. PMID: 30644390, PMCID: PMC6333924, DOI: 10.1038/s41467-018-08168-9.
- Striatal dopamine regulates systemic glucose metabolism in humans and miceTer Horst KW, Lammers NM, Trinko R, Opland DM, Figee M, Ackermans MT, Booij J, van den Munckhof P, Schuurman PR, Fliers E, Denys D, DiLeone RJ, la Fleur SE, Serlie MJ. Striatal dopamine regulates systemic glucose metabolism in humans and mice. Science Translational Medicine 2018, 10 PMID: 29794060, DOI: 10.1126/scitranslmed.aar3752.
- Innate Fear-Induced Weight Regulation in the C57BL/6J MouseGenné-Bacon EA, Trinko JR, DiLeone RJ. Innate Fear-Induced Weight Regulation in the C57BL/6J Mouse. Frontiers In Behavioral Neuroscience 2016, 10: 132. PMID: 27458352, PMCID: PMC4930939, DOI: 10.3389/fnbeh.2016.00132.
- The vitamin D metabolites 25(OH)D and 1,25(OH)2D are not related to either glucose metabolism or insulin action in obese womenHorst K, Versteeg RI, Gilijamse PW, Ackermans MT, Heijboer AC, Romijn JA, la Fleur SE, Trinko R, DiLeone RJ, Serlie MJ. The vitamin D metabolites 25(OH)D and 1,25(OH)2D are not related to either glucose metabolism or insulin action in obese women. Diabetes & Metabolism 2016, 42: 416-423. PMID: 27262368, DOI: 10.1016/j.diabet.2016.04.011.
- Activity of D1/2 Receptor Expressing Neurons in the Nucleus Accumbens Regulates Running, Locomotion, and Food IntakeZhu X, Ottenheimer D, DiLeone RJ. Activity of D1/2 Receptor Expressing Neurons in the Nucleus Accumbens Regulates Running, Locomotion, and Food Intake. Frontiers In Behavioral Neuroscience 2016, 10: 66. PMID: 27147989, PMCID: PMC4828436, DOI: 10.3389/fnbeh.2016.00066.
- Optogenetic stimulation of infralimbic PFC reproduces ketamine’s rapid and sustained antidepressant actionsFuchikami M, Thomas A, Liu R, Wohleb ES, Land BB, DiLeone RJ, Aghajanian GK, Duman RS. Optogenetic stimulation of infralimbic PFC reproduces ketamine’s rapid and sustained antidepressant actions. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 8106-8111. PMID: 26056286, PMCID: PMC4491758, DOI: 10.1073/pnas.1414728112.
- Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndromeXu M, Kobets A, Du JC, Lennington J, Li L, Banasr M, Duman RS, Vaccarino FM, DiLeone RJ, Pittenger C. Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 893-898. PMID: 25561540, PMCID: PMC4311862, DOI: 10.1073/pnas.1419533112.
- Optogenetic inhibition of neurons by internal light productionLand BB, Brayton CE, Furman KE, LaPalombara Z, DiLeone RJ. Optogenetic inhibition of neurons by internal light production. Frontiers In Behavioral Neuroscience 2014, 8: 108. PMID: 24744708, PMCID: PMC3978322, DOI: 10.3389/fnbeh.2014.00108.
- Prefrontal D1 dopamine signaling is required for temporal controlNarayanan 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: 20726-20731. PMID: 23185016, PMCID: PMC3528521, DOI: 10.1073/pnas.1211258109.
- Gene Profiling Reveals a Role for Stress Hormones in the Molecular and Behavioral Response to Food RestrictionGuarnieri 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: 358-365. PMID: 21855858, PMCID: PMC3237832, DOI: 10.1016/j.biopsych.2011.06.028.