Cell Type-Specific Loss of BDNF Signaling Mimics Optogenetic Control of Cocaine Reward

• Published in: Science (American Association for the Advancement of Science) Vol. 330; no. 6002; pp. 385 - 390
• Main Authors: Lobo, Mary Kay, Covington, Herbert E. III, Chaudhury, Dipesh, Friedman, Allyson K, Sun, HaoSheng, Damez-Werno, Diane, Dietz, David M, Zaman, Samir, Koo, Ja Wook, Kennedy, Pamela J, Mouzon, Ezekiell, Mogri, Murtaza, Neve, Rachael L, Deisseroth, Karl, Han, Ming-Hu, Nestler, Eric J
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for the Advancement of Science 15.10.2010; The American Association for the Advancement of Science
• Subjects: Animals; Behavior, Animal - drug effects; Biological and medical sciences; Brain-Derived Neurotrophic Factor - metabolism; Cellular biology; Channelrhodopsins; Cocaine; Cocaine - pharmacology; Cocaine-Related Disorders - metabolism; Conditioning (Psychology); Down regulation; Fetal cocaine exposure; Fundamental and applied biological sciences. Psychology; Inductive reasoning; Light; Locomotion; Medical sciences; Messenger RNA; Mice; Mice, Transgenic; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Models, Biological; Motor Activity - drug effects; Neurons; Neurons - metabolism; Neuropharmacology; Neurosciences; Nucleus Accumbens - cytology; Nucleus Accumbens - metabolism; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Receptor, trkB - genetics; Receptor, trkB - metabolism; Receptors; Receptors, Dopamine D1 - metabolism; Receptors, Dopamine D2 - metabolism; Reward; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sensitization; Signal Transduction; Vertebrates: nervous system and sense organs; CNS stimulant; Psychotropic; Central nervous system; D1 Dopamine receptor; Electrophysiology; Projection; Basal ganglion; Encephalon; Nucleus accumbens; Signal transduction; D2 Dopamine receptor; Cell death; Dopaminergic neuron; Drug of abuse; Cocaine; trkB receptor; Brain derived neurotrophic factor; Reward; Biological receptor
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1188472

The nucleus accumbens is a key mediator of cocaine reward, but the distinct roles of the two subpopulations of nucleus accumbens projection neurons, those expressing dopamine D1 versus D2 receptors, are poorly understood. We show that deletion of TrkB, the brain-derived neurotrophic factor (BDNF) receptor, selectively from D1+ or D2+ neurons oppositely affects cocaine reward. Because loss of TrkB in D2+ neurons increases their neuronal excitability, we next used optogenetic tools to control selectively the firing rate of D1+ and D2+ nucleus accumbens neurons and studied consequent effects on cocaine reward. Activation of D2+ neurons, mimicking the loss of TrkB, suppresses cocaine reward, with opposite effects induced by activation of D1+ neurons. These results provide insight into the molecular control of D1+ and D2+ neuronal activity as well as the circuit-level contribution of these cell types to cocaine reward.