Genetic evidence for the bidirectional modulation of synaptic plasticity in the prefrontal cortex by D1 receptors

• Yan-You Huang

  Center for Neurobiology and Behavior and Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, New York, NY 10032

• Eleanor Simpson

  Center for Neurobiology and Behavior and Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, New York, NY 10032

• Christoph Kellendonk

  Center for Neurobiology and Behavior and Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, New York, NY 10032

• Eric R. Kandel

  Center for Neurobiology and Behavior and Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, New York, NY 10032

抄録

To address the role of D1 receptors in the medial prefrontal cortex, we combined pharmacological and genetic manipulations to examine long-term synaptic potentiation (LTP)/long-term synaptic depression (LTD) in brain slices of rats and mice. We found that the D1 antagonist SCH23390 selectively blocked the maintenance but not the induction of LTP in the prefrontal cortex. Conversely, activation of D1 receptors facilitated the maintenance of LTP, and this effect is impaired in heterozygous D1 receptor knockout mice. Low-frequency stimulation induced a transient depression in the medial prefrontal cortex. This depression could be transformed into LTD by coapplication of dopamine. Coapplication of dopamine, however, shows no facilitating effect on LTD in heterozygous D1 receptor knockout mice. These results provide pharmacological and genetic evidence for a role of D1 receptors in the bidirectional modulation of synaptic plasticity in the medial prefrontal cortex. The absence of this modulation in heterozygous knockout mice shows that a dysregulation of dopamine receptor expression levels can have dramatic effects on synaptic plasticity in the prefrontal cortex.

収録刊行物

• Proceedings of the National Academy of Sciences

  Proceedings of the National Academy of Sciences 101 (9), 3236-3241, 2004-02-23

  Proceedings of the National Academy of Sciences

キーワード

• Multidisciplinary

詳細情報

• CRID: 1362544420337234816
• NII論文ID: 30016239534
• DOI: 10.1073/pnas.0308280101
• ISSN: 10916490
• ISSN: 00278424
• Web Site: https://pnas.org/doi/pdf/10.1073/pnas.0308280101
• データソース種別:
  • Crossref
  • CiNii Articles