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Constitutive knockout of the membrane cytoskeleton protein beta adducin decreases mushroom spine density in the nucleus accumbens but does not prevent spine remodeling in response to cocaine

Authors

  • Yonwoo Jung,

    1. Division of Molecular Psychiatry, Yale University School of Medicine, New Haven, CT, USA
    2. Interdepartmental Neuroscience Program, Yale University, New Haven, CT, USA
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    • These authors contributed equally.
  • Patrick J. Mulholland,

    1. Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA
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    • These authors contributed equally.
  • Shari L. Wiseman,

    1. Division of Molecular Psychiatry, Yale University School of Medicine, New Haven, CT, USA
    2. Interdepartmental Neuroscience Program, Yale University, New Haven, CT, USA
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  • L. Judson Chandler,

    1. Department of Neurosciences, Medical University of South Carolina, Charleston, SC, USA
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  • Marina R. Picciotto

    Corresponding author
    • Division of Molecular Psychiatry, Yale University School of Medicine, New Haven, CT, USA
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Correspondence: Marina R. Picciotto, as above

E-mail: marina.picciotto@yale.edu

Abstract

The adducin family of proteins associates with the actin cytoskeleton in a calcium-dependent manner. Beta adducin (βAdd) is involved in synaptic plasticity in the hippocampus; however, the role of βAdd in synaptic plasticity in other brain areas is unknown. Using diolistic labeling with the lipophilic dye DiI, we found that the density of mature mushroom-shaped spines was significantly decreased in the nucleus accumbens (NAc) in brain slices from βAdd-knockout (KO) mice as compared to their wildtype (WT) siblings. The effect of 10 days of daily cocaine (15 mg/kg) administration on NAc spine number and locomotor behavior was also measured in βAdd WT and KO mice. As expected, there was a significant increase in overall spine density in NAc slices from cocaine-treated WT mice at this time-point; however, there was a greater increase in the density of mushroom spines in βAdd-KO animals following chronic cocaine administration than in WT. In addition, βAdd-KO mice showed elevated locomotor activity in response to cocaine treatment compared to WT siblings. These results indicate that βAdd is required for stabilising mature spines under basal conditions in the NAc, but that lack of this protein does not prevent synaptic remodeling following repeated cocaine administration. In addition, these data are consistent with previous studies suggesting that βAdd may normally be involved in stabilising spines once drug- or experience-dependent remodeling has occurred.

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