Identification of NMDA receptor subunits contributing to midbrain dopaminergic learning and behavioural functions

鉴定有助于中脑多巴胺能学习和行为功能的 NMDA 受体亚基

• 批准号: BB/D015286/1
• 负责人: Susan Jones
• 金额: $ 36.74万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2006
• 资助国家: 英国
• 起止时间: 2006 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FD015286%2F1
• 关键词: Identification; NMDA; receptor; subunits; contributing

Many nerve cells in the brain communicate with each other by releasing chemicals known as neurotransmitters. Nerve cells depend on these chemical signals in order to carry out the functions of the brain, and any errors in neurotransmitter signalling can give rise to brain diseases, such as Parkinson's disease or drug addiction. One important neurochemical in the brain is the amino acid, glutamate. Glutamate is released from many nerve cells, and stimulates target cells by binding to receptor proteins specialised to recognise glutamate. Among the family of glutamate receptor proteins, one in particular is very interesting because it can have both beneficial effects and harmful effects on the brain. This receptor protein, known as the 'NMDA receptor', is required for the normal development of the brain from childhood to adulthood, and is also activated while the brain is learning and acquiring new information and memories. However, this receptor can be active under conditions that cause cells to die- this is known as neurodegeneration. Scientists have been interested in NMDA receptors for many years, and NMDA receptors have been identified and carefully characterised in several brain regions. However, one brain region where little is known about NMDA receptors is a set of nerve cells that are though to be important in controlling our movements, and in making us feel rewarded and motivated. These nerve cells release another important brain chemical known as dopamine. They are believed to be affected in several brain diseases, including Parkinson's disease, schizophrenia and drug addiction. NMDA receptors are believed to have an important role in controlling the behaviour of dopamine nerve cells, but at present, we do not know which kinds of NMDA receptors are found here, or what beneficial or harmful effects NMDA receptors have on these cells. This project aims to characterise NMDA receptors in dopamine nerve cells, and to link the activity of NMDA receptors to a simple behavioural learning process. Not only will the results from this project provide new information about how NMDA receptors are involved in the normal function of dopamine nerve cells, but it might reveal new NMDA receptor targets for developing therapies in some of the brain diseases mentioned.

大脑中的许多神经细胞通过释放被称为神经递质的化学物质来相互交流。神经细胞依赖这些化学信号来执行大脑的功能，神经递质信号的任何错误都可能导致大脑疾病，如帕金森病或药物成瘾。大脑中一种重要的神经化学物质是氨基酸，谷氨酸盐。谷氨酸从许多神经细胞中释放出来，并通过与专门识别谷氨酸的受体蛋白结合来刺激靶细胞。在谷氨酸受体蛋白家族中，有一种特别有趣，因为它对大脑既有有益的影响，也有有害的影响。这种受体蛋白被称为“NMDA受体”，是大脑从童年到成年的正常发育所必需的，并且在大脑学习和获取新信息和记忆时也被激活。然而，这种受体可以在导致细胞死亡的条件下活跃-这被称为神经变性。多年来，科学家们一直对NMDA受体感兴趣，并且NMDA受体已经在几个大脑区域中被鉴定和仔细表征。然而，我们对NMDA受体知之甚少的一个大脑区域是一组神经细胞，它们在控制我们的运动，让我们感到奖励和动力方面很重要。这些神经细胞释放另一种重要的大脑化学物质，称为多巴胺。他们被认为是影响了几种脑部疾病，包括帕金森氏症，精神分裂症和药物成瘾。NMDA受体被认为在控制多巴胺神经细胞的行为方面具有重要作用，但目前，我们不知道在这里发现了哪种NMDA受体，或者NMDA受体对这些细胞有什么有益或有害的影响。该项目旨在研究多巴胺神经细胞中的NMDA受体，并将NMDA受体的活性与简单的行为学习过程联系起来。该项目的结果不仅将提供有关NMDA受体如何参与多巴胺神经细胞正常功能的新信息，而且可能揭示新的NMDA受体靶点，用于开发上述某些脑部疾病的治疗方法。

项目成果

Functional heterogeneity of NMDA receptors in rat substantia nigra pars compacta and reticulata neurones.

• DOI: 10.1111/j.1460-9568.2010.07298.x
• 发表时间: 2010-08
• 期刊: The European journal of neuroscience
• 作者: Suárez F;Zhao Q;Monaghan DT;Jane DE;Jones S;Gibb AJ
• 通讯作者: Gibb AJ