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The Use of DREADDs (Designer Receptors Exclusively Activated by Designer Receptors) in Transgenic Mouse Behavioral Models

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Designer Receptors Exclusively Activated by Designer Drugs

Part of the book series: Neuromethods ((NM,volume 108))

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Abstract

Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are increasingly used to manipulate activity in specific neuronal populations in the brains of awake, behaving mice. Here we review the pros and cons of DREADDs relative to other genetically encoded neuromodulation technologies and describe in detail methods for using DREADDs with transgenic mouse behavioral models. This approach can not only provide insight into the role of specific neural circuits in behavior but also identify potential neuromodulation targets for the treatment of neuropsychiatric disorders.

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References

  1. Armbruster BN, Li X, Pausch MH, Herlitze S, Roth BL (2007) Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand. Proc Natl Acad Sci U S A 104:5163–5168, published online EpubMar (10.1073/pnas.0700293104)

    Article  PubMed Central  PubMed  Google Scholar 

  2. Alexander GM, Rogan SC, Abbas AI, Armbruster BN, Pei Y, Allen JA, Nonneman RJ, Hartmann J, Moy SS, Nicolelis MA, McNamara JO, Roth BL (2009) Remote control of neuronal activity in transgenic mice expressing evolved G protein-coupled receptors. Neuron 63:27–39, published online EpubJul (10.1016/j.neuron.2009.06.014)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Ferguson SM, Eskenazi D, Ishikawa M, Wanat MJ, Phillips PE, Dong Y, Roth BL, Neumaier JF (2011) Transient neuronal inhibition reveals opposing roles of indirect and direct pathways in sensitization. Nat Neurosci 14:22–24, published online EpubJan (10.1038/nn.2703)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Farrell MS, Pei Y, Wan Y, Yadav PN, Daigle TL, Urban DJ, Lee HM, Sciaky N, Simmons A, Nonneman RJ, Huang XP, Hufeisen SJ, Guettier JM, Moy SS, Wess J, Caron MG, Calakos N, Roth BL (2013) A Gαs DREADD mouse for selective modulation of cAMP production in striatopallidal neurons. Neuropsychopharmacology 38:854–862, published online EpubApr (10.1038/npp.2012.251)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Cassataro D, Bergfeldt D, Malekian C, Van Snellenberg JX, Thanos PK, Fishell G, Sjulson L (2014) Reverse pharmacogenetic modulation of the nucleus accumbens reduces ethanol consumption in a limited access paradigm. Neuropsychopharmacology 39:283–290, published online EpubJan (10.1038/npp.2013.184)

    Article  PubMed Central  PubMed  Google Scholar 

  6. Krashes MJ, Koda S, Ye C, Rogan SC, Adams AC, Cusher DS, Maratos-Flier E, Roth BL, Lowell BB (2011) Rapid, reversible activation of AgRP neurons drives feeding behavior in mice. J Clin Invest 121:1424–1428, published online EpubApr (10.1172/JCI46229)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Zhan C, Zhou J, Feng Q, Zhang JE, Lin S, Bao J, Wu P, Luo M (2013) Acute and long-term suppression of feeding behavior by POMC neurons in the brainstem and hypothalamus, respectively. J Neurosci 33:3624–3632, published online EpubFeb (10.1523/JNEUROSCI.2742-12.2013)

    Article  CAS  PubMed  Google Scholar 

  8. Sasaki K, Suzuki M, Mieda M, Tsujino N, Roth B, Sakurai T (2011) Pharmacogenetic modulation of orexin neurons alters sleep/wakefulness states in mice. PLoS One 6:e20360, 10.1371/journal.pone.0020360)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Gerfen CR, Paletzki R, Heintz N (2013) GENSAT BAC cre-recombinase driver lines to study the functional organization of cerebral cortical and basal ganglia circuits. Neuron 80:1368–1383, published online EpubDec (10.1016/j.neuron.2013.10.016)

    Article  CAS  PubMed  Google Scholar 

  10. Murray AJ, Sauer JF, Riedel G, McClure C, Ansel L, Cheyne L, Bartos M, Wisden W, Wulff P (2011) Parvalbumin-positive CA1 interneurons are required for spatial working but not for reference memory. Nat Neurosci 14:297–299, published online EpubMar (10.1038/nn.2751)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Sim S, Antolin S, Lin CW, Lin Y, Lin YX, Lois C (2013) Increased cell-intrinsic excitability induces synaptic changes in new neurons in the adult dentate gyrus that require Npas4. J Neurosci 33:7928–7940, published online EpubMay (10.1523/JNEUROSCI.1571-12.2013)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. De Marco García NV, Karayannis T, Fishell G (2011) Neuronal activity is required for the development of specific cortical interneuron subtypes. Nature 472:351–355, published online EpubApr (10.1038/nature09865)

    Article  PubMed Central  PubMed  Google Scholar 

  13. Yu CR, Power J, Barnea G, O'Donnell S, Brown HE, Osborne J, Axel R, Gogos JA (2004) Spontaneous neural activity is required for the establishment and maintenance of the olfactory sensory map. Neuron 42:553–566

    Google Scholar 

  14. Sjulson L, Miesenböck G (2008) Photocontrol of neural activity: biophysical mechanisms and performance in vivo. Chem Rev 108:1588–1602, published online EpubMay (10.1021/cr078221b)

    Article  CAS  PubMed  Google Scholar 

  15. Fenno L, Yizhar O, Deisseroth K (2011) The development and application of optogenetics. Annu Rev Neurosci 34:389–412, 10.1146/annurev-neuro-061010-113817)

    Article  CAS  PubMed  Google Scholar 

  16. Magnus CJ, Lee PH, Atasoy D, Su HH, Looger LL, Sternson SM (2011) Chemical and genetic engineering of selective ion channel-ligand interactions. Science 333:1292–1296, published online EpubSep (10.1126/science.1206606)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Tan EM, Yamaguchi Y, Horwitz GD, Gosgnach S, Lein ES, Goulding M, Albright TD, Callaway EM (2006) Selective and quickly reversible inactivation of mammalian neurons in vivo using the Drosophila allatostatin receptor. Neuron 51:157–170, published online EpubJul (10.1016/j.neuron.2006.06.018)

    Article  CAS  PubMed  Google Scholar 

  18. Chen SC, Ehrhard P, Goldowitz D, Smeyne RJ (1997) Developmental expression of the GIRK family of inward rectifying potassium channels: implications for abnormalities in the weaver mutant mouse. Brain Res 778:251–264

    Google Scholar 

  19. Ray RS, Corcoran AE, Brust RD, Kim JC, Richerson GB, Nattie E, Dymecki SM (2011) Impaired respiratory and body temperature control upon acute serotonergic neuron inhibition. Science 333:637–642, published online EpubJul (10.1126/science.1205295)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Garner AR, Rowland DC, Hwang SY, Baumgaertel K, Roth BL, Kentros C, Mayford M (2012) Generation of a synthetic memory trace. Science 335:1513–1516, published online EpubMar (10.1126/science.1214985)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Dittgen T, Nimmerjahn A, Komai S, Licznerski P, Waters J, Margrie TW, Helmchen F, Denk W, Brecht M, Osten P (2004) Lentivirus-based genetic manipulations of cortical neurons and their optical and electrophysiological monitoring in vivo. Proc Natl Acad Sci U S A 101:18206–18211, published online EpubDec (10.1073/pnas.0407976101)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Nathanson JL, Yanagawa Y, Obata K, Callaway EM (2009) Preferential labeling of inhibitory and excitatory cortical neurons by endogenous tropism of adeno-associated virus and lentivirus vectors. Neuroscience 161:441–450, published online EpubJun (10.1016/j.neuroscience.2009.03.032)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Atasoy D, Aponte Y, Su HH, Sternson SM (2008) A FLEX switch targets Channelrhodopsin-2 to multiple cell types for imaging and long-range circuit mapping. J Neurosci 28:7025–7030, published online EpubJul (10.1523/JNEUROSCI.1954-08.2008)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Cardin JA, Carlén M, Meletis K, Knoblich U, Zhang F, Deisseroth K, Tsai LH, Moore CI (2009) Driving fast-spiking cells induces gamma rhythm and controls sensory responses. Nature 459:663–667, published online EpubJun (10.1038/nature08002)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Gradinaru V, Zhang F, Ramakrishnan C, Mattis J, Prakash R, Diester I, Goshen I, Thompson KR, Deisseroth K (2010) Molecular and cellular approaches for diversifying and extending optogenetics. Cell 141:154–165, published online EpubApr (10.1016/j.cell.2010.02.037)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Kremer EJ, Boutin S, Chillon M, Danos O (2000) Canine adenovirus vectors: an alternative for adenovirus-mediated gene transfer. J Virol 74:505–512

    Google Scholar 

  27. Hnasko TS, Perez FA, Scouras AD, Stoll EA, Gale SD, Luquet S, Phillips PE, Kremer EJ, Palmiter RD (2006) Cre recombinase-mediated restoration of nigrostriatal dopamine in dopamine-deficient mice reverses hypophagia and bradykinesia. Proc Natl Acad Sci U S A 103:8858–8863, published online EpubJun (10.1073/pnas.0603081103)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Znamenskiy P, Zador AM (2013) Corticostriatal neurons in auditory cortex drive decisions during auditory discrimination. Nature 497:482–485, published online EpubMay (10.1038/nature12077)

    Article  CAS  PubMed  Google Scholar 

  29. Mahler SV, Vazey EM, Beckley JT, Keistler CR, McGlinchey EM, Kaufling J, Wilson SP, Deisseroth K, Woodward JJ, Aston-Jones G (2014) Designer receptors show role for ventral pallidum input to ventral tegmental area in cocaine seeking. Nat Neurosci, published online EpubMar (10.1038/nn.3664)

    Google Scholar 

  30. Saunders A, Johnson CA, Sabatini BL (2012) Novel recombinant adeno-associated viruses for Cre activated and inactivated transgene expression in neurons. Front Neural Circuits 6:47. doi:10.3389/fncir.2012.00047

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Cetin A, Komai S, Eliava M, Seeburg PH, Osten P (2006) Stereotaxic gene delivery in the rodent brain. Nat Protoc 1:3166–3173. doi:10.1038/nprot.2006.450

    Article  CAS  PubMed  Google Scholar 

  32. Guenthner CJ, Miyamichi K, Yang HH, Heller HC, Luo L (2013) Permanent genetic access to transiently active neurons via TRAP: targeted recombination in active populations. Neuron 78:773–784, published online EpubJun (10.1016/j.neuron.2013.03.025)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the Leon Levy Neuroscience Fellowship, NYU Physician Scientist Training Program, and NCATS grant UL1 TR000038.

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Authors and Affiliations

  1. Department of Neuroscience and Physiology, NYU School of Medicine, New York, NY, USA

    Daniela Cassataro

  2. Departments of Psychiatry and Neuroscience and Physiology, NYU School of Medicine, 450 E. 29th st, 9th Floor, New York, NY, 10016, USA

    Lucas Sjulson

Authors
  1. Daniela Cassataro
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  2. Lucas Sjulson
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Corresponding author

Correspondence to Lucas Sjulson .

Editor information

Editors and Affiliations

  1. Department of Medical Biochemistry and Molecular Biology, University of Saarland Medical Faculty, Homburg, Germany

    Gerald Thiel

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Cassataro, D., Sjulson, L. (2015). The Use of DREADDs (Designer Receptors Exclusively Activated by Designer Receptors) in Transgenic Mouse Behavioral Models. In: Thiel, G. (eds) Designer Receptors Exclusively Activated by Designer Drugs. Neuromethods, vol 108. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2944-3_6

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  • DOI: https://doi.org/10.1007/978-1-4939-2944-3_6

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2943-6

  • Online ISBN: 978-1-4939-2944-3

  • eBook Packages: Springer Protocols

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