The role of astrocytes in experience dependent plasticity

星形胶质细胞在经验依赖性可塑性中的作用

• 批准号: BB/J017809/1
• 负责人: Harri Parri
• 金额: $ 42.28万
• 依托单位: Aston University
• 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=BB%2FJ017809%2F1
• 关键词: role; astrocytes; experience; dependent; plasticity

We sense the features of our external world using special types of cells, such as those that can detect light for vision, sound for hearing or pressure for touch. The signals from these cells are sent along nerve fibres to the brain's cerebral cortex, where the information carried from our sensory cells is deciphered and "presented to us" as sensations of vision, hearing or touch. In the middle of the last century it was discovered that the connections between nerve cells in the cortex were not permanently fixed but could be modified, either by changes to the activity of the special sensory cells, but also due to brain damage. It became clear that these cortex changes were part of the brain's adaptation to changes in the environment. Soon after, similar changes were found elsewhere in the brain and it was realised that these processes were similar to the changes in nerve cell interconnections which occur during learning and in memory. This has become known as 'plasticity' and it is vital to understand its mechanisms, as this is key to understanding how the brain retains information. Moreover, if we understand the mechanisms of plasticity we may also be able to control brain plasticity. We believe that the ability to manipulate plasticity will enable us to improve learning and memory as well as offer new way of "repairing" the brain after damage, caused by either accident, stroke or epilepsy. For mice or rats, in contrast to humans, the sense of vision is not very well developed, so in every day life they rely on touch and use their whiskers to recognise subtle features of their immediate environment. Hence, a large part of rodents' cortex is devoted to receiving and deciphering the signals from the whiskers. For many years scientists have been investigating plastic changes that happen to nerve connections in the cortex when some, or all of the rodent's whiskers are cut, and a lot of progress has been made in understanding the mechanisms involved. In recent years however it has been realised that apart from nerve cells, there are also other types of cells in the brain that could be involved in the mechanisms of nerve cell plasticity. Interest has focused especially on a type of brain cell called an astrocyte, as it was discovered that astrocytes can transmit and receive signals to and from nerve cells. Importantly, we have recently found that astrocytes can also undergo plastic changes; therefore it is essential to understand how important astrocytic plasticity is to nerve cell plasticity in the cortex of living animals. In our experiments we will therefore cut whiskers and measure the extent of plastic changes happening to astrocytes compared to those happening to nerve cells and whether blocking or increasing astrocytic plasticity also modifies nerve cell plasticity. Finally, using a newly developed approach we can use optical stimulation to make the astrocytes undergo plasticity and so can test if that process in turn affects nerve cell plasticity. Improved understanding of how astrocytes are involved in neuronal plasticity will not only shed light on how our brain retains information, but will also lay a foundation for the development of new medical treatments that can help with memory loss and damage due to conditions such as stroke and Alzheimer's.

我们使用特殊类型的细胞来感知外部世界的特征，例如那些可以探测视觉的光、听觉的声音或触摸的压力的细胞。来自这些细胞的信号沿着神经纤维被发送到大脑的大脑皮层，从我们的感觉细胞携带的信息在那里被破译并以视觉、听觉或触觉的形式“呈现给我们”。上世纪中叶，人们发现大脑皮层神经细胞之间的连接不是永久固定的，而是可以改变的，既可以通过改变特殊感觉细胞的活动，也可以由于大脑损伤。很明显，这些皮质变化是大脑适应环境变化的一部分。不久之后，在大脑的其他部位也发现了类似的变化，人们意识到这些过程类似于学习和记忆过程中神经细胞相互连接的变化。这被称为“可塑性”，了解它的机制是至关重要的，因为这是理解大脑如何保存信息的关键。此外，如果我们了解可塑性的机制，我们也可能能够控制大脑的可塑性。我们相信，操纵可塑性的能力将使我们能够改善学习和记忆，并为因意外、中风或癫痫造成的大脑损伤提供新的修复方法。对于老鼠或大鼠来说，与人类相比，视觉不是很发达，所以在日常生活中，它们依靠触觉，并使用胡须来识别周围环境的细微特征。因此，啮齿动物大脑皮层的很大一部分专门用于接收和破译胡须发出的信号。多年来，科学家们一直在研究当啮齿动物的部分或全部胡须被剪断时，大脑皮质神经连接发生的可塑性变化，并在了解其中涉及的机制方面取得了许多进展。然而，近年来人们已经意识到，除了神经细胞，大脑中还有其他类型的细胞可能参与神经细胞可塑性的机制。人们的兴趣尤其集中在一种名为星形胶质细胞的脑细胞上，因为人们发现星形胶质细胞可以向神经细胞发送信号，并从神经细胞接收信号。重要的是，我们最近发现星形胶质细胞也可以经历可塑性变化；因此，了解星形胶质细胞可塑性对活体动物大脑皮层神经细胞可塑性的重要性是至关重要的。因此，在我们的实验中，我们将剪断胡须，并与神经细胞相比，测量星形胶质细胞发生可塑性变化的程度，以及阻止或增加星形胶质细胞的可塑性是否也会改变神经细胞的可塑性。最后，使用一种新开发的方法，我们可以使用光刺激来使星形胶质细胞经历可塑性，从而可以测试这一过程是否反过来影响神经细胞的可塑性。更好地了解星形胶质细胞是如何参与神经元可塑性的，不仅将有助于阐明我们的大脑是如何保留信息的，而且还将为开发新的医疗方法奠定基础，这些药物可以帮助治疗中风和阿尔茨海默氏症等疾病造成的记忆丧失和损伤。

项目成果

Astrocytes modulate thalamic sensory processing via mGlu2 receptor activation.

• DOI: 10.1016/j.neuropharm.2017.04.019
• 发表时间: 2017-07-15
• 期刊: Neuropharmacology
• 影响因子: 4.7
• 作者: Copeland CS;Wall TM;Sims RE;Neale SA;Nisenbaum E;Parri HR;Salt TE
• 通讯作者: Salt TE

Astrocyte-Mediated Neuronal Synchronization Properties Revealed by False Gliotransmitter Release.

• DOI: 10.1523/jneurosci.2761-16.2017
• 发表时间: 2017-10-11
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Pirttimaki TM;Sims RE;Saunders G;Antonio SA;Codadu NK;Parri HR
• 通讯作者: Parri HR

Astrocyte and Neuronal Plasticity in the Somatosensory System.

• DOI: 10.1155/2015/732014
• 发表时间: 2015
• 期刊: Neural plasticity
• 影响因子: 3.1
• 作者: Sims RE;Butcher JB;Parri HR;Glazewski S
• 通讯作者: Glazewski S