Cellular mechanisms of developmental plasticity in mouse primary visual cortex

我们如何看待世界取决于眼睛发出的视觉信息在大脑中的处理方式。在第一阶段，初级视皮层整合来自双眼的图像，这是立体视觉所必需的。与此同时，大脑该部分的神经元(神经细胞)具有检测线段和轮廓(水平、垂直等)的方向的能力，这构成了物体识别的基础。这种对线条方向的“调整”或敏感度部分是与生俱来的，部分是在童年的一个所谓的关键时期获得的。即使在成年，它仍然可以受到影响，例如，通过知觉训练。同样，双眼之间的平衡依赖于早期的视觉体验，如果这在某种程度上是非典型的视觉障碍，那么就会发生无法在以后的生活中纠正的视觉障碍。在这个项目中，我们想要研究小鼠初级视觉皮质中单个神经元的定向调节和双视性是如何受到早期视觉经验的影响和改变的，这种现象被称为发育可塑性。为此，动物将被饲养在只包含单一方向轮廓的视觉环境中，或者闭着一只眼睛。然后，我们将使用一种名为双光子成像的新的高分辨率大脑成像技术来记录单个神经细胞对视觉刺激的反应。这种活跃细胞发出荧光信号的技术甚至可以用来监测同一神经元随时间的反应。我们想用它来更多地了解发育可塑性背后的细胞机制。首先，通过使用转基因小鼠，我们可以区分两种主要类型的神经元(兴奋性和抑制性)，它们将以不同的颜色出现。我们将评估这两种细胞类型在可塑性中所起的作用。其次，我们知道某些基因对神经元之间的交流非常重要。我们将对缺乏两个特定基因的小鼠进行研究，以了解这些基因编码的蛋白质是否对发育可塑性至关重要。越来越明显的是，许多神经发育和神经精神疾病，如脆性X或精神分裂症，涉及神经细胞之间的通信缺陷。最终，我们希望更多地了解可塑性在正常情况下是如何工作的，将有助于我们更好地了解儿童发育障碍和老化大脑中的问题所在，并使我们能够制定治疗策略。

How we see the world depends on how visual information coming from the eyes is processed in the brain. At the first stage, the primary visual cortex integrates the images from the two eyes, which is essential for stereo vision. At the same time, neurons (nerve cells) in that part of the brain have the ability to detect the orientation of line segments and contours (horizontal, vertical, etc) which forms the basis for object recognition. This 'tuning' or sensitivity for line orientation is partly innate, and partly acquired during a so-called critical period in childhood. Even in adulthood, it can still be affected e.g. by perceptual training. Similarly, the balance between the two eyes depends on early visual experience, and if this is in some way atypical visual disorders will occur that cannot be corrected later in life. In this project, we want to investigate how the orientation tuning and binocularity of individual neurons in mouse primary visual cortex are influenced and altered by early visual experience, a phenomenon known as developmental plasticity. For this purpose, animals will be reared either in a visual environments which contains only contours of a single orientation, or with one eye closed. We will then record the responses of individual nerve cells to visual stimuli using a novel brain imaging technique of very high resolution called two-photon imaging. This technique in which active cells give off fluorescence signals can even be used to monitor the responses of the same neurons over time. We want to use it to find out more about the cellular mechanisms underlying developmental plasticity. First, by using genetically modified mice we can distinguish the two main types of neurons (excitatory and inhibitory ones) which will appear in different colours. We will assess what role these two cell types play in plasticity. Second, we know that certain genes are important for how neurons communicate with each other. We will study mice lacking two particular genes in order to see whether the proteins encoded by these genes are critical for developmental plasticity. It is becoming increasingly evident that many neurodevelopmental and neuropsychiatric diseases such as Fragile X or schizophrenia involve defects in the communication between nerve cells. Ultimately, we hope that knowing more about how plasticity works under normal circumstances will help us to better understand what goes wrong in childhood developmental disorders and in the ageing brain, and will enable us to develop treatment strategies.