4.4 Article

Altered corticostriatal neurotransmission and modulation in dopamine transporter knock-down mice

期刊

JOURNAL OF NEUROPHYSIOLOGY
卷 98, 期 1, 页码 423-432

出版社

AMER PHYSIOLOGICAL SOC
DOI: 10.1152/jn.00971.2006

关键词

-

资金

  1. NIMH NIH HHS [MH044894] Funding Source: Medline
  2. NINDS NIH HHS [NS33538] Funding Source: Medline

向作者/读者索取更多资源

Altered corticostriatal neurotransmission and modulation in dopamine transporter knockdown mice. J Neurophysiol 98: 423-432, 2007. First published May 23, 2007; doi: 10.1152/ jn. 00971.2006. Dopamine (DA) modulates glutamate neurotransmission in the striatum. Abnormal DA modulation has been implicated in neurological and psychiatric disorders. The development of DA transporter knock-down (DAT-KD) mice has permitted modeling of these disorders and has shed new light on DA modulation. DAT-KD mice exhibit increased extracellular DA, hyperactivity, and alterations in habituation. We used whole cell patch-clamp recordings from visually identified striatal neurons in slices to examine the effects of DAT- KD on corticostriatal transmission. Electrophysiological recordings from medium- sized spiny neurons in the dorsal striatum revealed alterations in both amplitude and frequency, of spontaneous glutamate receptor- mediated synaptic currents in cells from DAT- KD mice. Furthermore, kinetic analyses revealed that these currents had shorter half- amplitude durations and faster decay times. In contrast, GABA- receptor - mediated synaptic currents were not altered. Striatal neurons from DAT- KD mice also responded differently to amphetamine, cocaine, and DA D2- receptor agonists or antagonists compared with wildtype ( WT) littermate controls. In WTs amphetamine and cocaine reduced the frequency of spontaneous glutamate currents and these effects appeared to be mediated by activation of D2 receptors. In contrast, in DAT-KD mice either no changes or only small increases in frequency occurred. D2-receptor agonists or antagonists also had opposing effects in WT and DAT-KD mice. Together, these results indicate that chronically increased extracellular DA produces long-lasting changes in corticostriatal communication that may be mediated by changes in D2-receptor function. These findings have implications for understanding mechanisms underlying attention deficit hyperactivity disorder and Tourette's syndrome and may provide insights into novel therapeutic approaches.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.4
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据