Eating Disorders; Ethology; Neurobiology; Obesity; Psychiatry; Substance Abuse Detection; Natural History; Animal Nutrition Sciences
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 R-J, Gianessi CA, Brayton CE, Grimaldi DM, Sarhan M, Guarnieri DJ, Deisseroth K, Aghajanian GK, and RJ DiLeone (2014). Medial prefrontal D1 dopamine neurons control food intake. Nature Neuroscience, 17(2):248-53.
Optogenetic inhibition of neurons by internal light production
Land BB, Brayton CE, Furman KE, LaPalombara Z, and RJ DiLeone (2014). Optogenetic inhibition of neurons by internal light production. Frontiers in Behavioral Neuroscience: 8:108.
Prefrontal D1 dopamine signaling is required for temporal control
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.
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, and RJ DiLeone (2011) Gene profiling reveals a role for stress hormones in the molecular and behavioral response to food restriction.
Regulation of nucleus accumbens activity by the hypothalamic neuropeptide melanin-concentrating hormone
Sears, R.M., et al, (2010) Regulation of nucleus accumbens activity by the hypothalamic neuropeptide melanin-concentrating hormone. J. Neurosci. 30(24): 8263-8273.
Leptin receptor signaling in midbrain dopamine neurons regulates feeding
Hommel, J.D., et al. (2006). Leptin receptor signaling in midbrain dopamine neurons regulates feeding. Neuron 51(6):801-810.
Full List of PubMed Publications
- Maldonado-Avilés JG, Guarnieri DJ, Zhu X, DiLeone RJ: Down-regulation of miRNAs in the brain and development of diet-induced obesity. Int J Dev Neurosci. 2018 Feb; 2017 Jun 23. PMID: 28652200
- Keistler CR, Hammarlund E, Barker JM, Bond CW, DiLeone RJ, Pittenger C, Taylor JR: Regulation of Alcohol Extinction and Cue-Induced Reinstatement by Specific Projections among Medial Prefrontal Cortex, Nucleus Accumbens, and Basolateral Amygdala. J Neurosci. 2017 Apr 26; 2017 Mar 23. PMID: 28336571
- Narayanan NS, DiLeone RJ: Lip Sync: Gamma Rhythms Orchestrate Top-Down Control of Feeding Circuits. Cell Metab. 2017 Mar 7. PMID: 28273473
- Krystal JH, Abi-Dargham A, Akbarian S, Arnsten AFT, Barch DM, Bearden CE, Braff DL, Brown ES, Bullmore ET, Carlezon WA Jr, Carter CS, Cook EH Jr, Daskalakis ZJ, DiLeone RJ, Duman RS, Grace AA, Hariri AR, Harrison PJ, Hiroi N, Kenny PJ, Kleinman JE, Krystal AD, Lewis DA, Lipska BK, Marder SR, Mason GF, Mathalon DH, McClung CA, McDougle CJ, McIntosh AM, McMahon FJ, Mirnics K, Monteggia LM, Narendran R, Nestler EJ, Neumeister A, O'Donovan MC, Öngür D, Pariante CM, Paulus MP, Pearlson G, Phillips ML, Pine DS, Pizzagalli DA, Pletnikov MV, Ragland JD, Rapoport JL, Ressler KJ, Russo SJ, Sanacora G, Sawa A, Schatzberg AF, Shaham Y, Shamay-Tsoory SG, Sklar P, State MW, Stein MB, Strakowski SM, Taylor SF, Turecki G, Turetsky BI, Weissman MM, Zachariou V, Zarate CA Jr, Zubieta JK: Constance E. Lieber, Theodore R. Stanley, and the Enduring Impact of Philanthropy on Psychiatry Research. Biol Psychiatry. 2016 Jul 15. PMID: 27346079
- Genné-Bacon EA, Trinko JR, DiLeone RJ: Innate Fear-Induced Weight Regulation in the C57BL/6J Mouse. Front Behav Neurosci. 2016; 2016 Jul 4. PMID: 27458352
- Trinko JR, Land BB, Solecki WB, Wickham RJ, Tellez LA, Maldonado-Aviles J, de Araujo IE, Addy NA, DiLeone RJ: Vitamin D3: A Role in Dopamine Circuit Regulation, Diet-Induced Obesity, and Drug Consumption. eNeuro. 2016 Mar-Apr; 2016 May 19. PMID: 27257625
- Zhu X, Ottenheimer D, DiLeone RJ: Activity of D1/2 Receptor Expressing Neurons in the Nucleus Accumbens Regulates Running, Locomotion, and Food Intake. Front Behav Neurosci. 2016; 2016 Apr 12. PMID: 27147989
- D'Agostino G, Lyons DJ, Cristiano C, Burke LK, Madara JC, Campbell JN, Garcia AP, Land BB, Lowell BB, Dileone RJ, Heisler LK: Appetite controlled by a cholecystokinin nucleus of the solitary tract to hypothalamus neurocircuit. Elife. 2016 Mar 14; 2016 Mar 14. PMID: 26974347
- Anastasio NC, Stutz SJ, Fink LH, Swinford-Jackson SE, Sears RM, DiLeone RJ, Rice KC, Moeller FG, Cunningham KA: Serotonin (5-HT) 5-HT2A Receptor (5-HT2AR):5-HT2CR Imbalance in Medial Prefrontal Cortex Associates with Motor Impulsivity. ACS Chem Neurosci. 2015 Jul 15; 2015 Jul 7. PMID: 26120876
- Fuchikami 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. Proc Natl Acad Sci U S A. 2015 Jun 30; 2015 Jun 8. PMID: 26056286
- Dwyer JM, Maldonado-Avilés JG, Lepack AE, DiLeone RJ, Duman RS: Ribosomal protein S6 kinase 1 signaling in prefrontal cortex controls depressive behavior. Proc Natl Acad Sci U S A. 2015 May 12; 2015 Apr 27. PMID: 25918363
- van den Heuvel JK, Furman K, Gumbs MC, Eggels L, Opland DM, Land BB, Kolk SM, Narayanan NS, Fliers E, Kalsbeek A, DiLeone RJ, la Fleur SE: Neuropeptide Y activity in the nucleus accumbens modulates feeding behavior and neuronal activity. Biol Psychiatry. 2015 Apr 1; 2014 Jun 18. PMID: 25109664
- Xu 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. Proc Natl Acad Sci U S A. 2015 Jan 20; 2015 Jan 5. PMID: 25561540
- Taylor SR, Badurek S, Dileone RJ, Nashmi R, Minichiello L, Picciotto MR: GABAergic and glutamatergic efferents of the mouse ventral tegmental area. J Comp Neurol. 2014 Oct 1. PMID: 24715505
- Kim JD, Toda C, D'Agostino G, Zeiss CJ, DiLeone RJ, Elsworth JD, Kibbey RG, Chan O, Harvey BK, Richie CT, Savolainen M, Myöhänen T, Jeong JK, Diano S: Hypothalamic prolyl endopeptidase (PREP) regulates pancreatic insulin and glucagon secretion in mice. Proc Natl Acad Sci U S A. 2014 Aug 12; 2014 Jul 28. PMID: 25071172
- Ota KT, Liu RJ, Voleti B, Maldonado-Aviles JG, Duric V, Iwata M, Dutheil S, Duman C, Boikess S, Lewis DA, Stockmeier CA, DiLeone RJ, Rex C, Aghajanian GK, Duman RS: REDD1 is essential for stress-induced synaptic loss and depressive behavior. Nat Med. 2014 May; 2014 Apr 13. PMID: 24728411
- Land BB, Brayton CE, Furman KE, Lapalombara Z, Dileone RJ: Optogenetic inhibition of neurons by internal light production. Front Behav Neurosci. 2014; 2014 Apr 1. PMID: 24744708
- Maldonado-Avilés JG, Dileone RJ: Inhaling: endocannabinoids and food intake. Nat Neurosci. 2014 Mar. PMID: 24569827
- 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. Nat Neurosci. 2014 Feb; 2014 Jan 19. PMID: 24441680
- Arendt DH, Hassell J, Li H, Achua JK, Guarnieri DJ, Dileone RJ, Ronan PJ, Summers CH: Anxiolytic function of the orexin 2/hypocretin A receptor in the basolateral amygdala. Psychoneuroendocrinology. 2014 Feb; 2013 Oct 30. PMID: 24485472
- Anastasio NC, Stutz SJ, Fox RG, Sears RM, Emeson RB, DiLeone RJ, O'Neil RT, Fink LH, Li D, Green TA, Moeller FG, Cunningham KA: Functional status of the serotonin 5-HT2C receptor (5-HT2CR) drives interlocked phenotypes that precipitate relapse-like behaviors in cocaine dependence. Neuropsychopharmacology. 2014 Jan; 2013 Aug 13. PMID: 23939424
- Tellez LA, Ferreira JG, Medina S, Land BB, DiLeone RJ, de Araujo IE: Flavor-independent maintenance, extinction, and reinstatement of fat self-administration in mice. Biol Psychiatry. 2013 May 1. PMID: 23587200
- Udo T, Grilo CM, Brownell KD, Weinberger AH, Dileone RJ, McKee SA: Modeling the effects of positive and negative mood on the ability to resist eating in obese and non-obese individuals. Eat Behav. 2013 Jan; 2012 Oct 31. PMID: 23265400
- Guarnieri DJ, DiLeone RJ: Transcriptional plasticity in the brain following metabolic challenge. Neuropsychopharmacology. 2013 Jan. PMID: 23147479
- DiLeone RJ, Taylor JR, Picciotto MR: The drive to eat: comparisons and distinctions between mechanisms of food reward and drug addiction. Nat Neurosci. 2012 Oct; 2012 Sep 25. PMID: 23007187
- Land BB, DiLeone RJ: Losing the lust for life: a new role for an old feeding Peptide? Neuron. 2012 Aug 9. PMID: 22884320
- D'Sa C, Dileone RJ, Anderson GM, Sinha R: Serum and plasma brain-derived neurotrophic factor (BDNF) in abstinent alcoholics and social drinkers. Alcohol. 2012 May; 2012 Feb 22. PMID: 22364688
- 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. Biol Psychiatry. 2012 Feb 15. PMID: 21855858
- D'Sa C, Fox HC, Hong AK, Dileone RJ, Sinha R: Increased serum brain-derived neurotrophic factor is predictive of cocaine relapse outcomes: a prospective study. Biol Psychiatry. 2011 Oct 15; 2011 Jul 8. PMID: 21741029
- Gearhardt AN, Grilo CM, DiLeone RJ, Brownell KD, Potenza MN: Can food be addictive? Public health and policy implications. Addiction. 2011 Jul; 2011 Feb 14. PMID: 21635588
- Mineur YS, Abizaid A, Rao Y, Salas R, DiLeone RJ, Gündisch D, Diano S, De Biasi M, Horvath TL, Gao XB, Picciotto MR: Nicotine decreases food intake through activation of POMC neurons. Science. 2011 Jun 10. PMID: 21659607
- Trinko R, Gan G, Gao XB, Sears RM, Guarnieri DJ, DiLeone RJ: Erk1/2 mediates leptin receptor signaling in the ventral tegmental area. PLoS One. 2011; 2011 Nov 4. PMID: 22076135
- Okamoto H, Voleti B, Banasr M, Sarhan M, Duric V, Girgenti MJ, Dileone RJ, Newton SS, Duman RS: Wnt2 expression and signaling is increased by different classes of antidepressant treatments. Biol Psychiatry. 2010 Sep 15; 2010 Jun 8. PMID: 20570247
- 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. J Neurosci. 2010 Jun 16. PMID: 20554878
- Sharf R, Sarhan M, Brayton CE, Guarnieri DJ, Taylor JR, DiLeone RJ: Orexin signaling via the orexin 1 receptor mediates operant responding for food reinforcement. Biol Psychiatry. 2010 Apr 15; 2010 Feb 26. PMID: 20189166
- Sharf R, Guarnieri DJ, Taylor JR, DiLeone RJ: Orexin mediates morphine place preference, but not morphine-induced hyperactivity or sensitization. Brain Res. 2010 Mar 4; 2009 Dec 23. PMID: 20034477
- Sharf R, Sarhan M, Dileone RJ: Role of orexin/hypocretin in dependence and addiction. Brain Res. 2010 Feb 16; 2009 Aug 20. PMID: 19699189
- Narayanan NS, Guarnieri DJ, DiLeone RJ: Metabolic hormones, dopamine circuits, and feeding. Front Neuroendocrinol. 2010 Jan; 2009 Oct 28. PMID: 19836414
- Gourley SL, Howell JL, Rios M, DiLeone RJ, Taylor JR: Prelimbic cortex bdnf knock-down reduces instrumental responding in extinction. Learn Mem. 2009 Dec; 2009 Nov 19. PMID: 19926781
- DiLeone RJ: Leptin: taking the path less traveled. Cell Metab. 2009 Aug. PMID: 19656482
- Sharf R, Sarhan M, Dileone RJ: Orexin mediates the expression of precipitated morphine withdrawal and concurrent activation of the nucleus accumbens shell. Biol Psychiatry. 2008 Aug 1; 2008 Apr 18. PMID: 18423425
- Guarnieri DJ, DiLeone RJ: MicroRNAs: a new class of gene regulators. Ann Med. 2008. PMID: 18382885
- Trinko R, Sears RM, Guarnieri DJ, DiLeone RJ: Neural mechanisms underlying obesity and drug addiction. Physiol Behav. 2007 Aug 15; 2007 Jan 16. PMID: 17292426
- Chao JR, Ni YG, Bolaños CA, Rahman Z, DiLeone RJ, Nestler EJ: Characterization of the mouse adenylyl cyclase type VIII gene promoter: regulation by cAMP and CREB. Eur J Neurosci. 2002 Oct. PMID: 12405989