Template neuronal networks in developing neocortex

发育中新皮质的模板神经元网络

• 批准号: MR/J013188/1
• 负责人: Michael Ashby
• 金额: $ 60万
• 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: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FJ013188%2F1
• 关键词: Template; neuronal; networks; developing; neocortex

When we are young our brains develop rapidly in response to experiences we encounter. This determines how it will function throughout our lives. One example is that young children are able to learn languages easily compared to adults; young minds are very adaptable. My research is geared towards understanding the processes going on in the young brain that make it adaptable. Nerve cells, or neurons, form the circuits that do the computation that underlies brain function. Early in our lives, nature and nurture combine to influence the way the neurons become connected together into circuits in the brain. Nature's role works through the genetically-encoded processes that build basic brain structure. This basic structure acts as a template for the nurture part, as the experiences we encounter cause changes in the basic template structure. These changes allow the brain to work properly. Surprisingly, we know very little about the basic structure of template circuits that develop before sensory experiences then adjust them. However, it is very important to understand these templates because their properties will determine how much our experiences can influence brain function. In one sense, the properties of this basic structure define just how big the differences between individual brains can be. This study is specifically designed to investigate how and when the earliest template circuits form in the young brain and how they influence the nurture-dependent phase of brain circuit development. Nerve cells communicate through structures called synapses. When a circuit changes, such as when we learn a language, it is largely because its synapses change. Likewise, when a circuit is wired up incorrectly, as in certain neurological disorders like autism, it is likely that the synapses are at fault. Therefore, to understand early template circuits, we must measure the synapses that connect it all together. Also, there are likely to be changes in those synapses that are important for development of the template circuit. Measurement of changes in circuit structure is not easy because there are millions of synapses that are all mixed together. So, it is difficult to find which circuit they belong to. I have developed a new technique to locate which nerve cells are connected and to analyse the synapses that connect them. This techniques uses a special type of microscopy that can see deep inside brain tissue with very fine detail. This approach will be used to measure the properties of synapses and neurons within template circuits as they develop early in life.

当我们年轻的时候，我们的大脑会对我们遇到的经历做出快速的反应。这决定了它将如何在我们的生活中发挥作用。一个例子是，与成年人相比，幼儿能够轻松学习语言;年轻的头脑适应性很强。我的研究旨在了解年轻大脑中使其适应性的过程。神经细胞，或神经元，形成了大脑功能基础上的计算电路。在我们生命的早期，先天和后天的联合收割机影响着神经元连接在一起形成大脑回路的方式。大自然的作用是通过构建基本大脑结构的遗传编码过程来实现的。这个基本结构就像是培养部分的模板，因为我们遇到的经历会导致基本模板结构的变化。这些变化使大脑能够正常工作。令人惊讶的是，我们对模板回路的基本结构知之甚少，这些回路在感官体验之前发展，然后调整它们。然而，理解这些模板是非常重要的，因为它们的属性将决定我们的经历对大脑功能的影响程度。从某种意义上说，这种基本结构的特性决定了个体大脑之间的差异有多大。这项研究旨在研究最早的模板回路如何以及何时在年轻的大脑中形成，以及它们如何影响大脑回路发育的养育依赖阶段。神经细胞通过称为突触的结构进行交流。当一个回路发生变化时，比如当我们学习一种语言时，很大程度上是因为它的突触发生了变化。同样地，当一个回路连接不正确时，就像某些神经系统疾病，如自闭症，很可能是突触出了问题。因此，为了了解早期的模板电路，我们必须测量将其连接在一起的突触。此外，那些对模板电路的发展很重要的突触也可能发生变化。测量电路结构的变化并不容易，因为有数百万个突触混合在一起。很难确定它们属于哪一种电路。我开发了一种新技术，可以定位哪些神经细胞连接在一起，并分析连接它们的突触。这种技术使用一种特殊类型的显微镜，可以看到脑组织内部非常精细的细节。这种方法将用于测量突触和神经元在生命早期发育时模板电路内的特性。

项目成果

Altered Synapse Stability in the Early Stages of Tauopathy.

• DOI: 10.1016/j.celrep.2017.03.013
• 发表时间: 2017-03-28
• 期刊: Cell reports
• 影响因子: 8.8
• 作者: Jackson JS;Witton J;Johnson JD;Ahmed Z;Ward M;Randall AD;Hutton ML;Isaac JT;O'Neill MJ;Ashby MC
• 通讯作者: Ashby MC

Convergent Metabotropic Signaling Pathways Inhibit SK Channels to Promote Synaptic Plasticity in the Hippocampus.

• DOI: 10.1523/jneurosci.1160-18.2018
• 发表时间: 2018-10-24
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Tigaret CM;Chamberlain SEL;Sadowski JHLP;Hall J;Ashby MC;Mellor JR
• 通讯作者: Mellor JR

A Bayesian predictive approach for dealing with pseudoreplication

• DOI: 10.1038/s41598-020-59384-7
• 发表时间: 2020-02-11
• 期刊: SCIENTIFIC REPORTS
• 影响因子: 4.6
• 作者: Lazic, Stanley E.;Mellor, Jack R.;Munafo, Marcus R.
• 通讯作者: Munafo, Marcus R.