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

大脑包含数十亿个专门的细胞，称为神经元，它们是神经系统中每个回路的基本组成部分。神经元的主要目的是传递信息：当它们从其他神经元接收到足够的输入时，它们会发送简短的电脉冲，称为动作电位，这使它们能够与其他神经元进行通信。一般来说，神经元分为两种类型：兴奋性神经元和抑制性中间神经元，兴奋性神经元使其他神经元更有可能激发动作电位，抑制性中间神经元使其他神经元不太可能激发动作电位。如果将大脑的电活动与音乐进行比较，那么兴奋性神经元为大脑的“音乐”提供音符，而抑制性中间神经元提供音符之间的停顿。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，就只有沉默，没有停顿，音乐就会变成不和谐的声音。最近的研究表明，痴呆症，如阿尔茨海默氏病，会导致抑制性中间神经元的功能障碍。对正常大脑功能的影响是严重的，并被认为转化为阿尔茨海默病中的认知和记忆障碍。来自我们实验室的数据表明，选择性地操纵抑制性中间神经元活动可以恢复阿尔茨海默病小鼠模型的正常脑功能。有趣的是，类似的拯救效果最近被归因于非侵入性的光和声刺激，频率与视频的帧速率（40 Hz）相似。一个是基础科学性质的：我们想确定在阿尔茨海默病小鼠模型中刺激抑制性中间神经元和传递光和声刺激后的拯救作用的机制。另一个目的是翻译性质：我们想看看在阿尔茨海默病小鼠模型中刺激抑制性中间神经元以及传递光和声刺激是否真的可以恢复阿尔茨海默病早期阶段的记忆功能。

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.