Restoring hippocampal-cortical circuit and memory dysfunction in prodromal Alzheimer's Disease.

恢复阿尔茨海默病前驱期的海马皮质回路和记忆功能障碍。

基本信息

批准号：
MR/T004363/1
负责人：
Michael Kohl
金额：
$ 38.32万
依托单位：
University of Glasgow
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2019
资助国家：
英国
起止时间：
2019 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=MR%2FT004363%2F1
关键词：
Restoring hippocampal cortical circuit memory

项目摘要

Brains contain billions of specialised cells, called neurons, which are the fundamental building blocks of every circuit in the nervous system. The principal purpose of a neuron is to transmit information: when they receive sufficient input from other neurons, they send brief electrical pulses, called action potentials, which allows them to communicate with other neurons. Broadly speaking, neurons exist as two types: excitatory neurons, which make other neurons more likely to fire action potentials, and inhibitory interneurons, which make other neurons less likely to fire action potentials. If one were to compare the brain's electrical activity to music, then excitatory neurons provide the notes for the brain's 'music', whilst inhibitory interneurons provide the pauses between notes. All computations in the brain require very precise synchrony between different neurons: without the notes, there would be only silence, and without the pauses, the music would become a cacophony.Recent research has shown that dementias, such as Alzheimer's Disease, cause a dysfunction in inhibitory interneurons. The resulting effects on normal brain function are severe and thought to translate to the cognitive and memory impairments seen in Alzheimer's Disease. Data from our labs shows that selectively manipulating inhibitory interneuron activity can restore normal brain function in mouse models of Alzheimer's Disease. Intriguingly, a similar rescuing effect has recently been attribute to non-invasive light and acoustic stimulation at frequencies similar to the frame rate of video (40 Hz).Our project has two aims. One is of a basic science nature: We would like to determine the mechanisms underlying the rescue effects following stimulation of inhibitory interneurons and delivery of light and acoustic stimuli in mouse models of Alzheimer's Disease. The other aim is of a translational nature: We would like to see whether stimulation of inhibitory interneurons and delivery of light and acoustic stimuli in mouse models of Alzheimer's Disease can actually restore memory function in the early stages of Alzheimer's Disease.

大脑包含数十亿个专门细胞，称为神经元，这是神经系统中每个电路的基本构建块。神经元的主要目的是传输信息：当它们从其他神经元中收到足够的输入时，它们会发送简短的电脉冲，称为动作电位，这使他们可以与其他神经元进行通信。从广义上讲，神经元作为两种类型存在：兴奋性神经元，这使其他神经元更有可能发射动作电位，以及抑制性神经元，这使得其他神经元发射动作电位的可能性较小。如果要将大脑的电活动与音乐进行比较，则兴奋性神经元为大脑的“音乐”提供了音符，而抑制性中间神经元之间的抑制作用则可以在音符之间停下来。大脑中的所有计算都需要不同神经元之间非常精确的同步：没有音符，只会有沉默，如果没有停顿，音乐就会变成一场刺激性。当时的研究表明，痴呆症，例如阿尔茨海默氏病，会导致功能障碍，从而引起功能障碍在抑制性中间神经元中。对正常脑功能的结果影响很严重，并被认为转化为阿尔茨海默氏病中的认知和记忆障碍。来自我们实验室的数据表明，在阿尔茨海默氏病小鼠模型中，有选择地操纵抑制性中间神经元的活性可以恢复正常的脑功能。有趣的是，最近在类似于视频帧速率（40 Hz）的频率下，类似的救援效果归因于非侵入性的光和声刺激。您的项目具有两个目标。一种是基本的科学性质：我们想确定抑制性中间神经元刺激后救援效应的机制，以及在阿尔茨海默氏病小鼠模型中的光和声刺激的传递。另一个目的是转化性质：我们希望看看在阿尔茨海默氏病小鼠模型中刺激抑制性中间神经元以及光和声刺激是否可以在阿尔茨海默氏病的早期阶段恢复记忆功能。