RSK2 信号在脑缰核对场所厌恶学习的贡献。
RSK2 signaling in brain habenula contributes to place aversion learning.
机构信息
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique/Institut National de la Santé et de la Recherche Médicale/Université de Strasbourg, 67404 Illkirch, France.
出版信息
Learn Mem. 2011 Aug 18;18(9):574-8. doi: 10.1101/lm.2221011. Print 2011 Sep.
Abstract
RSK2 is a Ser/Thr kinase acting in the Ras/MAPK pathway. Rsk2 gene deficiency leads to the Coffin-Lowry Syndrome, notably characterized by cognitive deficits. We found that mrsk2 knockout mice are unable to associate an aversive stimulus with context in a lithium-induced conditioned place aversion task requiring both high-order cognition and emotional processing. Virally mediated shRNA-RSK2 knockdown in the habenula, whose involvement in cognition is receiving increasing attention, also ablated contextual conditioning. RSK2 signaling in the habenula, therefore, is essential for this task. Our study reveals a novel role for RSK2 in cognitive processes and uncovers the critical implication of an intriguing brain structure in place aversion learning.
摘要
RSK2 是一种丝氨酸/苏氨酸激酶，作用于 Ras/MAPK 通路。RSK2 基因缺失会导致 Coffin-Lowry 综合征，其特征主要为认知缺陷。我们发现 mrsk2 基因敲除小鼠无法将厌恶刺激与环境联系起来，无法完成锂诱导的条件性位置厌恶任务，而该任务需要高级认知和情绪处理。在海蚌核内通过病毒介导的 shRNA-RSK2 敲低，也消除了环境条件的形成。海蚌核内的 RSK2 信号对于这个任务是必需的。我们的研究揭示了 RSK2 在认知过程中的新作用，并揭示了这个引人关注的脑结构在位置厌恶学习中的关键作用。
相似文献
1
RSK2 signaling in brain habenula contributes to place aversion learning.RSK2 信号在脑缰核对场所厌恶学习的贡献。
Learn Mem. 2011 Aug 18;18(9):574-8. doi: 10.1101/lm.2221011. Print 2011 Sep.
2
RSK2 signaling in medial habenula contributes to acute morphine analgesia.中缝背核的 RSK2 信号转导参与急性吗啡镇痛。
Neuropsychopharmacology. 2012 Apr;37(5):1288-96. doi: 10.1038/npp.2011.316. Epub 2012 Jan 4.
3
Altered ERK/MAPK signaling in the hippocampus of the mrsk2_KO mouse model of Coffin-Lowry syndrome.Coffin-Lowry 综合征 mrsk2_KO 小鼠模型中海马细胞中 ERK/MAPK 信号转导的改变。
J Neurochem. 2011 Nov;119(3):447-59. doi: 10.1111/j.1471-4159.2011.07423.x. Epub 2011 Sep 28.
4
Defective synaptic transmission and structure in the dentate gyrus and selective fear memory impairment in the Rsk2 mutant mouse model of Coffin-Lowry syndrome.Rsk2 突变型 Coffin-Lowry 综合征小鼠模型中齿状回突触传递和结构缺陷以及选择性恐惧记忆损伤。
Neurobiol Dis. 2013 Oct;58:156-68. doi: 10.1016/j.nbd.2013.05.016. Epub 2013 Jun 3.
5
Selective alteration of adult hippocampal neurogenesis and impaired spatial pattern separation performance in the RSK2-deficient mouse model of Coffin-Lowry syndrome.RSK2 缺陷型 Coffin-Lowry 综合征小鼠模型中海马神经发生的选择性改变及空间模式分离能力受损。
Neurobiol Dis. 2018 Jul;115:69-81. doi: 10.1016/j.nbd.2018.04.007. Epub 2018 Apr 6.
6
RSK2 is a modulator of craniofacial development.RSK2 是颅面发育的调节剂。
PLoS One. 2014 Jan 8;9(1):e84343. doi: 10.1371/journal.pone.0084343. eCollection 2014.
7
Rsk2 Knockout Affects Emotional Behavior in the IntelliCage.Rsk2基因敲除影响智能笼中的情绪行为。
Behav Genet. 2017 Jul;47(4):434-448. doi: 10.1007/s10519-017-9853-3. Epub 2017 Jun 6.
8
p90 ribosomal S6 kinase 2 exerts a tonic brake on G protein-coupled receptor signaling.p90核糖体S6激酶2对G蛋白偶联受体信号传导施加持续性抑制作用。
Proc Natl Acad Sci U S A. 2006 Mar 21;103(12):4717-22. doi: 10.1073/pnas.0600585103. Epub 2006 Mar 10.
9
Expression analysis of RSK gene family members: the RSK2 gene, mutated in Coffin-Lowry syndrome, is prominently expressed in brain structures essential for cognitive function and learning.RSK基因家族成员的表达分析：在科芬-洛里综合征中发生突变的RSK2基因，在对认知功能和学习至关重要的脑结构中显著表达。
Hum Mol Genet. 2002 Nov 1;11(23):2929-40. doi: 10.1093/hmg/11.23.2929.
10
Deletion of the Coffin-Lowry syndrome gene Rsk2 in mice is associated with impaired spatial learning and reduced control of exploratory behavior.小鼠中Coffin-Lowry综合征基因Rsk2的缺失与空间学习能力受损和探索行为控制能力降低有关。
Behav Genet. 2007 Jan;37(1):31-50. doi: 10.1007/s10519-006-9116-1. Epub 2006 Oct 11.
引用本文的文献
1
Habenula alterations in resting state functional connectivity among autistic individuals.自闭症个体静息态功能连接中的缰核改变。
bioRxiv. 2025 May 14:2025.05.14.653992. doi: 10.1101/2025.05.14.653992.
2
RSK1 and RSK2 as therapeutic targets: an up-to-date snapshot of emerging data.核糖體S6激酶1和核糖體S6激酶2作為治療靶點：新興數據的最新概述
Expert Opin Ther Targets. 2024 Dec;28(12):1047-1059. doi: 10.1080/14728222.2024.2433123. Epub 2024 Dec 4.
3
Chronic tianeptine induces tolerance in analgesia and hyperlocomotion via mu-opioid receptor activation in mice.慢性服用噻奈普汀通过激活小鼠体内的μ-阿片受体诱导镇痛耐受性和运动亢进。
Front Psychiatry. 2023 May 23;14:1186397. doi: 10.3389/fpsyt.2023.1186397. eCollection 2023.
4
Reduced dopamine release in Dcc haploinsufficiency male mice abolishes the rewarding effects of cocaine but not those of morphine and ethanol.Dcc 杂合不足雄性小鼠多巴胺释放减少可消除可卡因的奖赏效应，但不影响吗啡和乙醇的奖赏效应。
Psychopharmacology (Berl). 2023 Mar;240(3):637-646. doi: 10.1007/s00213-022-06288-1. Epub 2022 Dec 6.
5
Effects of single and dual hypocretin-receptor blockade or knockdown of hypocretin projections to the central amygdala on alcohol drinking in dependent male rats.单次和双重食欲素受体阻断或向杏仁核中央核投射的食欲素基因敲低对酒精依赖雄性大鼠饮酒行为的影响。
Addict Neurosci. 2022 Sep;3. doi: 10.1016/j.addicn.2022.100028. Epub 2022 Jul 3.
6
Recent advances in basic science methodology to evaluate opioid safety profiles and to understand opioid activities.评估阿片类药物安全性概况及了解阿片类药物活性的基础科学方法的最新进展。
Fac Rev. 2021 Feb 19;10:15. doi: 10.12703/r/10-15. eCollection 2021.
7
Habenula GPR139 is associated with fear learning in the zebrafish.缰核 GPR139 与斑马鱼的恐惧学习有关。
Sci Rep. 2021 Mar 10;11(1):5549. doi: 10.1038/s41598-021-85002-1.
8
Control of aversion by glycine-gated GluN1/GluN3A NMDA receptors in the adult medial habenula.甘氨酸门控 GluN1/GluN3A NMDA 受体在成年内侧缰核中控制厌恶反应。
Science. 2019 Oct 11;366(6462):250-254. doi: 10.1126/science.aax1522.
9
Animal Models for Coffin-Lowry Syndrome: RSK2 and Nervous System Dysfunction.科芬-洛里综合征的动物模型：RSK2与神经系统功能障碍
Front Behav Neurosci. 2018 May 23;12:106. doi: 10.3389/fnbeh.2018.00106. eCollection 2018.
10
RSK Influences the Pace of the Circadian Clock by Negative Regulation of Protein Kinase Shaggy Activity.核糖体S6激酶通过负调控蛋白激酶Shaggy的活性影响生物钟的节奏。
Front Mol Neurosci. 2018 Apr 13;11:122. doi: 10.3389/fnmol.2018.00122. eCollection 2018.
本文引用的文献
1
Deletion of the δ opioid receptor gene impairs place conditioning but preserves morphine reinforcement.δ 阿片受体基因缺失损害位置条件反射，但保留吗啡强化。
Biol Psychiatry. 2011 Apr 1;69(7):700-3. doi: 10.1016/j.biopsych.2010.10.021. Epub 2010 Dec 17.
2
The habenula is crucial for experience-dependent modification of fear responses in zebrafish.缰核对于斑马鱼依赖经验的恐惧反应的修饰至关重要。
Nat Neurosci. 2010 Nov;13(11):1354-6. doi: 10.1038/nn.2654. Epub 2010 Oct 10.
3
Coffin-Lowry syndrome: a role for RSK2 in mammalian neurogenesis.考芬-洛里综合征：RSK2 在哺乳动物神经发生中的作用。
Dev Biol. 2010 Nov 15;347(2):348-59. doi: 10.1016/j.ydbio.2010.08.035. Epub 2010 Sep 8.
4
The habenula: from stress evasion to value-based decision-making.缰核：从逃避压力到基于价值的决策。
Nat Rev Neurosci. 2010 Jul;11(7):503-13. doi: 10.1038/nrn2866.
5
Nicotinic receptors in the habenula: importance for memory.缰核中的烟碱型乙酰胆碱受体：对记忆的重要性。
Neuroscience. 2010 Mar 17;166(2):386-90. doi: 10.1016/j.neuroscience.2009.12.035. Epub 2009 Dec 24.
6
Coffin-Lowry syndrome.考芬-洛里综合征。
Eur J Hum Genet. 2010 Jun;18(6):627-33. doi: 10.1038/ejhg.2009.189. Epub 2009 Nov 4.
7
Nicotinic receptors in the habenulo-interpeduncular system are necessary for nicotine withdrawal in mice.缰核-脚间系统中的烟碱型受体对小鼠尼古丁戒断是必需的。
J Neurosci. 2009 Mar 11;29(10):3014-8. doi: 10.1523/JNEUROSCI.4934-08.2009.
8
The RSK family of kinases: emerging roles in cellular signalling.RSK激酶家族：在细胞信号传导中的新作用。
Nat Rev Mol Cell Biol. 2008 Oct;9(10):747-58. doi: 10.1038/nrm2509.
9
A conductor hidden in the orchestra? Role of the habenular complex in monoamine transmission and cognition.隐藏在管弦乐队中的指挥？缰核复合体在单胺能传递和认知中的作用。
Neurosci Biobehav Rev. 2007;31(5):658-72. doi: 10.1016/j.neubiorev.2007.01.004. Epub 2007 Feb 12.
10
Deletion of the Coffin-Lowry syndrome gene Rsk2 in mice is associated with impaired spatial learning and reduced control of exploratory behavior.小鼠中Coffin-Lowry综合征基因Rsk2的缺失与空间学习能力受损和探索行为控制能力降低有关。
Behav Genet. 2007 Jan;37(1):31-50. doi: 10.1007/s10519-006-9116-1. Epub 2006 Oct 11.
Zotero 插件