Neurobehavioral phenotyping of G(αq) knockout mice reveals impairments in motor functions and spatial working memory without changes in anxiety or behavioral despair.
Neurobehavioral phenotyping of G(αq) knockout mice reveals impairments in motor functions and spatial working memory without changes in anxiety or behavioral despair.
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DOI：
10.3389/fnbeh.2012.00029
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发表时间：
2012
影响因子：
3
通讯作者：
Stanwood GD
中科院分区：
文献类型：
--
作者：
Frederick AL;Saborido TP;Stanwood GD
许多神经递质、激素和感觉刺激通过靶向激活与GαQ家族异源三聚体G蛋白偶联的受体来诱导它们的细胞反应。然而，我们仍然对失去这种信号活动对大脑功能的影响知之甚少。因此，我们在一系列行为测试中检测了编码GαQ的基因GNAQ的遗传失活对反应性的影响，以评估GαQ信号在大脑回路中的作用，这些回路介导情感行为(焦虑和行为绝望)、空间工作记忆和运动输出(协调、强度、自发活动和药物诱导的反应)的表达。首先，我们重复和扩展了研究结果，显示在GαQ基因敲除小鼠中存在明显的运动缺陷，这是通过加速转杆和倒屏测试进行评估的。然后，我们通过对精神刺激剂可卡因、苯扎西平D1受体激动剂SKF83822和SKF83959以及NMDA受体拮抗剂MK-801的药物诱导运动反应的开场测试和分析，评估了基底节运动环对这些损伤的贡献。我们观察到多巴胺能激动剂而不是MK-801基因敲除的GαQ基因敲除小鼠的药物诱导的运动活动显著增加，这表明在没有GαQ的情况下，基底节运动回路基本完好无损。此外，我们在升高的零迷宫和强迫游泳测试中观察到正常的表型，表明在GNAQ表达缺失后，焦虑和抑郁相关的回路似乎基本完好无损。最后，使用Y迷宫揭示了GαQ基因敲除小鼠的空间记忆缺陷，这表明通过GαQ的受体信号在这些回路中是熟练执行这项任务所必需的。
Many neurotransmitters, hormones, and sensory stimuli elicit their cellular responses through the targeted activation of receptors coupled to the Gαq family of heterotrimeric G proteins. Nevertheless, we still understand little about the consequences of loss of this signaling activity on brain function. We therefore examined the effects of genetic inactivation of Gnaq, the gene that encode for Gαq, on responsiveness in a battery of behavioral tests in order to assess the contribution of Gαq signaling capacity in the brain circuits mediating expression of affective behaviors (anxiety and behavioral despair), spatial working memory, and locomotor output (coordination, strength, spontaneous activity, and drug-induced responses). First, we replicated and extended findings showing clear motor deficits in Gαq knockout mice as assessed on an accelerating rotarod and the inverted screen test. We then assessed the contribution of the basal ganglia motor loops to these impairments, using open field testing and analysis of drug-induced locomotor responses to the psychostimulant cocaine, the benzazepine D1 receptor agonists SKF83822 and SKF83959, and the NMDA receptor antagonist MK-801. We observed significant increases in drug-induced locomotor activity in Gαq knockout mice from the dopaminergic agonists but not MK-801, indicating that basal ganglia locomotor circuitry is largely intact in the absence of Gαq. Additionally, we observed normal phenotypes in both the elevated zero maze and the forced swim test indicating that anxiety and depression-related circuitry appears to be largely intact after loss of Gnaq expression. Lastly, use of the Y-maze revealed spatial memory deficits in Gαq knockout mice, indicating that receptors signaling through Gαq are necessary in these circuits for proficiency in this task.
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影响因子：
5
作者：
ARNT, J;HYTTEL, J;SANCHEZ, C
通讯作者：
SANCHEZ, C
影响因子：
10.6
作者：
Arnsten, Amy F. T.
通讯作者：
Arnsten, Amy F. T.
影响因子：
5
作者：
Andringa, G;Drukarch, B;Stoof, JC
通讯作者：
Stoof, JC
影响因子：
3.4
作者：
GNANALINGHAM, KK;HUNTER, AJ;MARSDEN, CD
通讯作者：
MARSDEN, CD
DOI：
10.1073/pnas.1009874107
发表时间：
2010-08-17
影响因子：
11.1
作者：
Bateup, Helen S.;Santini, Emanuela;Greengard, Paul
通讯作者：
Greengard, Paul