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

GABA能抑制在人类双眼视觉系统功能和功能障碍中的作用

• 批准号: MR/V034723/1
• 负责人: Holly Bridge
• 金额: $ 126.53万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FV034723%2F1
• 关键词: role; GABAergic; inhibition; function; dysfunction

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.

当你在半空中接球，或用手指按下按钮时，你正在使用你的深度感。最精确的深度感觉，被称为‘双目’深度，来自我们的双眼一起使用。脸部前面的两只眼睛允许两种视角，其中一种视角相对于另一种视角略微偏向一侧。在幼年时期，大脑学会了将这两个图像结合起来，形成一个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，并提供同样清晰的图像。如果两只眼睛指向不同的方向，或者一只眼睛的图像非常模糊，孩子们可能会形成一只眼睛比另一只眼睛工作得更好的“懒眼”。这会导致弱视被大脑忽视。懒眼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因为大脑中一种名为GABA的神经化学物质。GABA是一种抑制性神经化学物质，这意味着它可以削弱来自其他脑细胞的信号。我们认为，GABA会削弱“懒眼”发出的信号，因为它不如另一只眼有用。更广泛地说，GABA可能会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在双眼深度的观看方式来做到这一点。我们将使用大脑扫描仪和一种被称为磁共振光谱学的方法来测量活着的人脑中的GABA。我们的目标是通过三项研究来确定GABA在双目视觉中的重要性。在研究1中，目标是测试用处方药氯巴扎姆增加GABA是否能改善双眼深度知觉。总的来说，这也可能使脑细胞对视觉输入更具选择性。为了确保任何差异完全是由于药物造成的，我们还将要求相同的参与者在另一天重复实验时服用安慰剂药片。将药物数据与安慰剂数据进行比较，将揭示GABA增加的贡献。在研究2中，我们将训练患有懒视眼的成年人学习一起使用他们的眼睛，在两周的时间里，每天执行一小时的视觉任务。这已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水平是否与训练的改善有关，以及大脑中发生活动变化的地方。在最后的研究中，我们将招募6-13岁有发展懒眼风险的儿童。这样的孩子通常会在他们强壮的眼睛上戴上6个月的贴片，每天几个小时，试图防止懒眼的发展。这种“遮盖疗法”帮助弱眼更好地工作，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30名儿童，以及年龄匹配的视力健康的儿童，以测试贴片疗法是否改变了视觉大脑中的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。了解补片疗法塑造儿童大脑的方式可以改进未来的治疗方案。这一系列研究的重点是GABA在大脑中的作用，这将使我们能够设计有助于改善儿童和成人双眼视觉的治疗方法。

项目成果

Mapping the visual world to the human brain.

• DOI: 10.7554/elife.75171
• 发表时间: 2021-12-03
• 期刊: eLife
• 影响因子: 7.7
• 作者: Ip B;Bridge H
• 通讯作者: Bridge H

Intra-Areal Visual Topography in Primate Brains Mapped with Probabilistic Tractography of Diffusion-Weighted Imaging.

• DOI: 10.1093/cercor/bhab364
• 发表时间: 2022-06-07
• 期刊: Cerebral cortex (New York, N.Y. : 1991)

GABA and Glutamate in hMT+ Link to Individual Differences in Residual Visual Function After Occipital Stroke.

• DOI: 10.1161/strokeaha.123.043269
• 发表时间: 2023-09
• 期刊: Stroke
• 影响因子: 8.3

Investigating the human binocular visual system using multi-modal magnetic resonance imaging.

使用多模态磁共振成像研究人类双眼视觉系统。

• DOI: 10.1177/03010066231178664
• 发表时间: 2023
• 期刊: Perception
• 影响因子: 1.7
• 作者: Bridge H

Event-related functional magnetic resonance spectroscopy.

• DOI: 10.1016/j.neuroimage.2023.120194
• 发表时间: 2023-08-01
• 期刊: NeuroImage
• 影响因子: 5.7
• 作者: Koolschijn RS;Clarke WT;Ip IB;Emir UE;Barron HC
• 通讯作者: Barron HC