The role of GABAergic inhibition in the function and dysfunction of the human binocular visual system

当你在半空中接住一个球，或者用手指按下一个按钮时，你正在使用你的深度感。最精确的深度感觉，称为“双眼”深度，来自我们两只眼睛的同时使用。面部前方的两只眼睛可以让人看到两个世界，其中一个视野相对于另一个略微向一侧偏移。在儿童早期，大脑学会将这两个图像结合起来，形成一个可以深入观察的单一图像。为了成功地做到这一点，眼睛必须指向同一个方向，并给出同样清晰的图像。如果眼睛指向不同的方向，或者一只眼睛的图像非常模糊，孩子们就会患上“懒眼”，即一只眼睛比另一只眼睛工作得更好。这导致较弱的眼睛被大脑忽略。弱视是儿童最常见的视力问题之一。科学家认为弱视被大脑忽视的原因之一是大脑中一种叫做GABA的神经化学物质。GABA是一种抑制性神经化学物质，这意味着它可以减弱来自其他脑细胞的信号。我们认为伽马氨基丁酸削弱了“懒眼”发出的信号，因为它没有另一只眼睛有用。更一般地说，GABA可能主动控制我们看到和看不到的东西。因此，了解GABA在视觉中的作用是很重要的。我们将通过测量大脑中GABA水平的变化如何改变我们的双眼深度来做到这一点。我们将使用脑部扫描仪和一种测量活人大脑中GABA的方法，即磁共振光谱法。我们的目的是通过三个研究来确定GABA在双目视觉中的重要性。在研究1中，目的是测试用处方药氯巴唑仑增加GABA是否能改善双眼深度感知。这也可能使脑细胞对视觉输入更有选择性。为了确保任何差异都是由药物引起的，我们还会让同样的参与者服用安慰剂，同时在另一天重复实验。比较药物和安慰剂的数据将揭示GABA增加的贡献。在研究2中，我们将训练弱视的成年人一起学习使用眼睛，每天进行一小时的视觉任务，持续两周。这已经被证明可以提高眼睛协同工作的能力。我们将测量训练前后的GABA水平，这将显示GABA水平是否与训练带来的改善有关，以及大脑中发生任何活动变化的地方。在最后的研究中，我们将招募6-13岁有弱视风险的儿童。这样的孩子通常会在6个月的时间里，每天在他们较强的眼睛上戴几个小时的眼罩，以防止弱视的发展。这种“遮挡疗法”有助于弱眼更好地工作，因为它是唯一能看到东西的眼睛，大脑被迫使用它的信号。我们将扫描其中的30名儿童，以及与年龄匹配的视力健康的儿童，以测试贴片疗法是否会改变视觉大脑中的GABA浓度。我们还将测试视力的改善是否与GABA水平的变化有关。了解修补疗法是如何塑造儿童大脑的，可以改善未来的治疗方案。这一系列专注于GABA在大脑中的作用的研究将使我们能够设计出帮助改善儿童和成人双眼视力的治疗方法。

When you catch a ball in mid-air, or point your finger to press a button, you are using your sensation of depth. The most precise sensation of depth, called 'binocular' depth, comes from using our two eyes together. The two eyes at the front of the face allow two views of the world, with one view slightly shifted to the side with respect to the other. During early childhood, the brain learns to combine these two images to form a single image seen in depth. To do this successfully, the eyes have to point in the same direction and give equally clear images. If the eyes point in different directions, or one eye gives a very blurry image, children can develop a 'lazy eye' where one eye works better than the other. This leads to the weaker eye being ignored by the brain. Lazy eye is one of the most common visual problem in children. Scientists think that one of the reasons why the weak eye is ignored by the brain is because of a neurochemical in the brain called GABA. GABA is an inhibitory neurochemical, which means that it can weaken the signal from other brain cells. We think that GABA weakens the signal from the 'lazy eye' because it is less useful than the other eye. More generally, GABA may actively control what we see and do not see. It is important, therefore, to understand the role of GABA in vision. We will do this by measuring how changing GABA levels in the brain change the way we see in binocular depth. We will use a brain scanner and a method to measure GABA in the living human brain, known as MR Spectroscopy. We aim to determine the importance of GABA in binocular vision using three studies. In Study 1, the goal is to test whether increasing GABA with a prescription drug, known as clobazam, improves binocular depth perception. This may also make brain cells more selective to visual input in general. To ensure that any differences are exclusively due to the drug, we will also ask the same participants to take a placebo pill while repeating the experiments on another day. Comparing drug to placebo data will reveal the contribution of the increase in GABA. In study 2, we will train adults with lazy eye to learn to use their eyes together, by performing a visual task for an hour each day for 2 weeks. This has been shown to improve the ability of the eyes to work together. We will measure the level of GABA before and after training, which will show whether GABA level is related to improvements due to training, and the places in the brain where any activity changes occurred. In the final study, we will recruit children aged 6-13 who are at risk of developing lazy eye. Such children usually wear a patch for 6 months over their stronger eye for several hours a day to try to prevent the development of lazy eye. This 'occlusion therapy' helps the weaker eye work better as it is the only eye that is seeing, and the brain is forced to use its signal. We will scan 30 of these children, along with age-matched children with healthy vision, to test whether patching therapy changes the GABA concentration in the visual brain. We will also test whether improvement in vision is related to changes in GABA levels. Understanding the way in which patching therapy shapes the child brain can improve future treatment regimes. This series of studies focusing on the role of GABA in the brain will allow us to design treatments to help improve binocular vision for children and adults.