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CREB modulates excitability of nucleus accumbens neurons

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Abstract

Drugs of abuse cause activation of the cyclic AMP response element binding protein (CREB) in the nucleus accumbens (NAc). Expression of active CREB in rat NAc medium spiny neurons (MSNs) increased their excitability, whereas dominant-negative CREB had the opposite effect. Decreasing excitability of NAc MSNs in vivo by overexpression of potassium channels enhanced locomotor responses to cocaine, suggesting that the increased NAc MSN excitability caused by CREB helped to limit behavioral sensitivity to cocaine.

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Figure 1: CREB influences excitability of MSNs in NAc slice cultures.
Figure 2: CREB influences ionic conductances in NAc MSNs in slice cultures and MSN excitability in vivo.
Figure 3: Decreasing NAc MSN excitability by the expression of the potassium channel subunit Kir2.1 enhances locomotor response to cocaine.

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Acknowledgements

We thank E. Sura and W. Ju for technical assistance and J. Trimmer, R.C. Yu and R. Axel for providing constructs. This work was supported by grants from the National Institute on Drug Abuse and the US National Institute of Mental Health.

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Nancy Pritzker Laboratory, Stanford University, Palo Alto, 94304, California, USA

    Yan Dong, Daniel Saal, Helene Marie & Robert C Malenka

  2. Department of Psychiatry and Center for Basic Neuroscience, The University of Texas Southwestern Medical Center, Dallas, 75390, Texas, USA

    Thomas Green & Eric J Nestler

  3. Department of Genetics and McClean Hospital, Harvard University, Cambridge, 02478, Massachusetts, USA

    Rachael Neve

Authors
  1. Yan Dong
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  2. Thomas Green
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  3. Daniel Saal
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  5. Rachael Neve
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  6. Eric J Nestler
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  7. Robert C Malenka
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Correspondence to Robert C Malenka.

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Supplementary information

Supplementary Table 1

Membrane properties of NAc medium spiny neurons in slice culture (PDF 68 kb)

Supplementary Table 2

Membrane properties of NAc medium spiny neurons in acute slices (PDF 69 kb)

Supplementary Methods (DOC 41 kb)

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Dong, Y., Green, T., Saal, D. et al. CREB modulates excitability of nucleus accumbens neurons. Nat Neurosci 9, 475–477 (2006). https://doi.org/10.1038/nn1661

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