Cell type - Specific loss of BDNF signaling mimics optogenetic control of cocaine reward

Mary Kay Lobo, Herbert E. Covington, Dipesh Chaudhury, Allyson K. Friedman, Hao Sheng Sun, Diane Damez-Werno, David M. Dietz, Samir Zaman, Ja Wook Koo, Pamela J. Kennedy, Ezekiell Mouzon, Murtaza Mogri, Rachael L. Neve, Karl Deisseroth, Ming Hu Han, Eric J. Nestler

    Research output: Contribution to journalArticle

    Abstract

    The nucleus accumbens is a keymediator 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.

    Original languageEnglish (US)
    Pages (from-to)385-390
    Number of pages6
    JournalScience
    Volume330
    Issue number6002
    DOIs
    StatePublished - Oct 15 2010

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    Optogenetics
    Brain-Derived Neurotrophic Factor
    Reward
    Cocaine
    Neurons
    Nucleus Accumbens
    trkB Receptor
    Dopamine

    ASJC Scopus subject areas

    • General

    Cite this

    Lobo, M. K., Covington, H. E., Chaudhury, D., Friedman, A. K., Sun, H. S., Damez-Werno, D., ... Nestler, E. J. (2010). Cell type - Specific loss of BDNF signaling mimics optogenetic control of cocaine reward. Science, 330(6002), 385-390. https://doi.org/10.1126/science.1188472

    Cell type - Specific loss of BDNF signaling mimics optogenetic control of cocaine reward. / Lobo, Mary Kay; Covington, Herbert E.; Chaudhury, Dipesh; Friedman, Allyson K.; Sun, Hao Sheng; 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.

    In: Science, Vol. 330, No. 6002, 15.10.2010, p. 385-390.

    Research output: Contribution to journalArticle

    Lobo, MK, Covington, HE, Chaudhury, D, Friedman, AK, Sun, HS, Damez-Werno, D, Dietz, DM, Zaman, S, Koo, JW, Kennedy, PJ, Mouzon, E, Mogri, M, Neve, RL, Deisseroth, K, Han, MH & Nestler, EJ 2010, 'Cell type - Specific loss of BDNF signaling mimics optogenetic control of cocaine reward', Science, vol. 330, no. 6002, pp. 385-390. https://doi.org/10.1126/science.1188472
    Lobo MK, Covington HE, Chaudhury D, Friedman AK, Sun HS, Damez-Werno D et al. Cell type - Specific loss of BDNF signaling mimics optogenetic control of cocaine reward. Science. 2010 Oct 15;330(6002):385-390. https://doi.org/10.1126/science.1188472
    Lobo, Mary Kay ; Covington, Herbert E. ; Chaudhury, Dipesh ; Friedman, Allyson K. ; Sun, Hao Sheng ; 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. / Cell type - Specific loss of BDNF signaling mimics optogenetic control of cocaine reward. In: Science. 2010 ; Vol. 330, No. 6002. pp. 385-390.
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