Abnormal interactions between the hippocampus and prefrontal cortex in rodent models of schizophrenia

精神分裂症啮齿动物模型中海马和前额皮质之间的异常相互作用

• 批准号: G0501146/1
• 负责人: Matt Jones
• 金额: $ 41.11万
• 依托单位: University of Bristol
• 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=G0501146%2F1
• 关键词: Abnormal; interactions; between; hippocampus; prefrontal

Brains are like orchestras. Both are subdivided into numerous, specialized sections with individual roles, yet the activity of all sections must be coordinated in order for the whole to function properly. Musicians in an orchestra keep time by following the lead of their conductor; by analogy, how do neurons of different brain regions coordinate their activity during the complex repertoire of behaviour?Electrophysiology allows us to record the electrical impulses through which neurons communicate. We find that many groups of neurons, like the sections of an orchestra, show rhythmic activity. Rhythms in connected neural networks are coordinated with one another, but only during behaviour that requires communication between the brain regions that contain them. Thus rhythmic activity can act as the brain?s conductor, allowing different groups of neurons to communicate with one another at different times. This study will use recordings from three brain regions involved in learning and memory and decision-making to see how they interact during behaviour. All three of the regions in question show signs of damage in schizophrenic patients. We suspect that the brain behaves like a ?cacophonous orchestra? during schizophrenia: a breakdown of coordinated timing leads to cognitive and behavioural abnormalities because different brain regions do not keep time with one another.We can model schizophrenia in rats and mice. For example, if we give animals drugs like ketamine (?Special K?), they develop behavioural problems like those in psychotic patients. By recording from the neurons of these animals, we can characterize the breakdown in coordinated neural activity that accompanies their breakdown in behaviour. Then, by comparing electrophysiology from these animal models with electrophysiology from the clinic (the impulses of human neurons can be recorded through the scalp as EEG, or ?brain waves?), we can begin to understand what goes wrong in the schizophrenic brain and, most importantly, begin to test therapies that will eventually put it right.

大脑就像管弦乐队。两者都被细分为众多的、具有各自角色的专门部门，但所有部门的活动必须协调一致，才能使整体正常运转。管弦乐队中的音乐家通过跟随指挥的指挥来保持节奏。以此类推，不同大脑区域的神经元在复杂的行为过程中如何协调其活动？电生理学使我们能够记录神经元交流的电脉冲。我们发现许多神经元组，就像管弦乐队的各个部分一样，表现出有节奏的活动。连接的神经网络中的节律是相互协调的，但仅限于需要在包含它们的大脑区域之间进行通信的行为期间。因此，有节奏的活动可以充当大脑的导体，允许不同的神经元组在不同的时间相互交流。这项研究将使用涉及学习、记忆和决策的三个大脑区域的记录来观察它们在行为过程中如何相互作用。精神分裂症患者的所有三个区域都显示出受损的迹象。我们怀疑大脑的行为就像一个“不和谐的管弦乐队”？精神分裂症期间：协调时间的崩溃会导致认知和行为异常，因为不同的大脑区域彼此不保持时间。我们可以在大鼠和小鼠中模拟精神分裂症。例如，如果我们给动物服用氯胺酮（？特殊K？）等药物，它们就会出现像精神病患者那样的行为问题。通过记录这些动物的神经元，我们可以表征伴随着它们行为崩溃的协调神经活动的崩溃。然后，通过将这些动物模型的电生理学与临床的电生理学进行比较（人类神经元的脉冲可以通过头皮记录为脑电图或“脑电波”），我们可以开始了解精神分裂症患者的大脑出了什么问题，最重要的是，开始测试最终将其纠正的疗法。