Distribution and molecular organisation of native kainate receptors in the mammalian central nervous system

神经递质受体是一种蛋白质，它允许中枢神经系统中的细胞有效而快速地进行通信。哺乳动物大脑中的绝大多数兴奋性神经递质受体是由氨基酸谷氨酸激活的。谷氨酸是以一种高度调节和活性依赖的方式从神经元释放出来的。有几种不同类别的受体可以对谷氨酸作出反应。其中最不典型的是红藻氨酸受体(KARs)。获得更多关于KARs的精确分布、分子和药理学特性的信息是很重要的，因为对调节它们的机制的深入了解将使它们参与正常的大脑功能得到更好的定义。此外，KARs还与神经疾病状态有关，它们的激活被证明具有潜在的神经毒性。最近，我们开发了一系列新的试剂(抗体)和药理工具，为选择性鉴定、分离和分析KARs创造了新的机会。我们的研究将利用这些新工具来提供关于KARs在成人和发育中大脑不同功能重要区域的分布和分子组成的基本信息。大脑的发育是一个复杂的过程，涉及数百万个神经元之间形成的连接。控制神经元连接发展的分子和细胞机制对正常的大脑功能至关重要。我们的研究将阐明KARS在神经元发育中的作用。先前的研究证实，感觉经验(例如：视觉经验)指导神经回路的发展。我们将检验卡尔斯受视觉经验影响的假设。拟议的研究结果可能有助于未来开发用于治疗癫痫等疾病的抗惊厥药物和/或对治疗中风和头部创伤等疾病有价值的神经保护药物。

Neurotransmitter receptors are proteins that allow cells in the central nervous system to communicate effectively and rapidly. The vast majority of excitatory neurotransmitter receptors in the mammalian brain are activated by the amino acid glutamate. Glutamate is released from neurons in a highly regulated and activity dependent manner. There are several different classes of receptors which respond to glutamate. The least well characterised of these are the kainate receptors (KARs). It is important to gain more information about the precise distribution, molecular and pharmacological properties of KARs, because increased understanding of the mechanisms that regulate them will allow their involvement in normal brain function to be better defined. In addition, KARs have been implicated in neurological disease states and their activation has been shown to be potently neurotoxic. Recently we have developed a range of new reagents (antibodies) and pharmacological tools which created new opportunities for the selective identification, isolation and analysis of KARs. Our research will exploit the availability of these new tools to provide basic information about the distribution and molecular composition of KARs in different functionally important regions of the adult and developing brain. The development of the brain is a complicated process involving millions of connections forming between neurons. The molecular and cellular mechanisms governing the development of neuronal connections are fundamentally important to normal brain function. Our studies will elucidate the role of KARs in neuronal development. Previous studies established that sensory experience (e.g.: visual experience) guides the development of neuronal circuits. We will test the hypothesis that KARs are influenced by visual experience. The results of the proposed studies may help the future development of therapeutic agents such as anticonvulsants for the treatment of diseases like epilepsy and/or neuroprotective drugs that could be of value for treating conditions such as stroke and head trauma.