4.5 Article

Modulation of Burst Firing of Neurons in Nucleus Reticularis of the Thalamus by GluN2C-Containing NMDA Receptors

期刊

MOLECULAR PHARMACOLOGY
卷 96, 期 2, 页码 193-203

出版社

AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
DOI: 10.1124/mol.119.116780

关键词

-

资金

  1. National Science Foundation [456818]
  2. National Institutes of Health National Institute of Neurologic Disorders and Stroke [NS104705]
  3. National Institute of Mental Health [MH116003]

向作者/读者索取更多资源

The GluN2C subunit of the NMDA receptor is enriched in the neurons in the nucleus reticularis of the thalamus (nRT), but its role in regulating their function is not well understood. We found that deletion of GluN2C subunit did not affect spike frequency in response to depolarizing current injection or hyperpolarization-induced rebound burst firing of nRT neurons. D-Cycloserine or CIQ (GluN2C/GluN2D positive allosteric modulator) did not affect the depolarization-induced spike frequency in nRT neurons. A newly identified highly potent and efficacious coagonist of GluN1/GluN2C NMDA receptors, AICP ((R)-2-amino-3-(4(2-ethylpheny1)-1H-indole-2-carboxannido)propanoic acid), was found to reduce the spike frequency and burst firing of nRT neurons in wild type but not GIuN2C knockout. This effect was potentially due to facilitation of GIuN2C-containing receptors, because inhibition of NMDA receptors by AP5 did not affect spike frequency in nRT neurons. We evaluated the effect of intracerebroventricular injection of AICP. AICP did not affect basal locomotion or prepulse inhibition but facilitated MK-801-induced hyperlocomotion. This effect was observed in wild-type but not in GIuN2C knockout mice, demonstrating that AICP produces GluN2C-selective effects in vivo. Using a chemogenetic approach, we examined the role of nRT in this behavioral effect. G(q)- or G(i)-coupled DREADDs were selectively expressed in nRT neurons using Cre-dependent viral vectors and PV-Cre mouse line. We found that similar to AICP effect, activation of G(q)- but not G(i)-coupled DREADD facilitated MK-801-induced hyperlocomotion. Together, these results identify a unique role of GluN2C-containing receptors in the regulation of nRT neurons and suggest GIuN2C-selective in vivo targeting of NMDA receptors by AICP.

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

4.5
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