How is diverse sensory information encoded within the simple circuitry of the thalamus?

科学界对大脑的基本了解仍然非常有限，无法提供全面治疗与年龄相关的认知能力下降和其他常见神经系统疾病的任何希望。为了充分了解控制我们大脑的基本机制，科学依赖于动物模型，使神经科学家能够研究这个最复杂器官的细胞和分子方面。在这个提议中，我们的目标是更好地理解视觉信息是如何被我们的大脑处理的。我们看到、听到和感觉到的一切都必须经过大脑中一个相对较小的部分——丘脑。几十年来，我们已经知道，丘脑的一个关键作用是将我们感觉世界的显著特征分布到我们大脑的外部部分，即新皮层，以实现更高层次的大脑功能，如感知、认知、运动命令的生成、空间推理和语言。重要的是，当我们睡觉时，丘脑停止将这种感觉信息传递给新皮层。这个过程中最重要的步骤之一是将一种叫做GABA（氨基丁酸）的小抑制分子与一种叫做GABA- a受体的膜结合蛋白结合。抑制性神经递质GABA通常从局部中间神经元释放，我们实验室的高分辨率成像研究表明，丘脑中间神经元主要位于丘脑的背外侧膝状核区域，该区域接收来自我们眼睛的感觉信息。因此，我们相信这些中间神经元在视觉中起着特殊的作用，但令人惊讶的是，我们不知道这个作用是什么。在大多数大脑区域，GABA的释放受到许多不同类型的中间神经元的控制，每个中间神经元的作用略有不同。例如，在视网膜上有超过60种类型的中间神经元，每一种都负责将视觉场景转化为传递给丘脑的电子信息。令人惊讶的是，丘脑中间神经元的多样性似乎要少得多，这就引发了一个有趣的问题：它们是如何处理来自视网膜的复杂信息的。为了解决这个问题，我们首先需要找出他们接收到的是什么类型的视觉信息。我们已经开发了一种创新的技术，通过使用新颖的示踪剂来标记这些丘脑中间神经元的输入。我们现在想用专门的设备来测量这些中间神经元的电活动，这些设备模仿它们在受到视觉刺激时的行为。我们现在处于一个独特的位置，能够发现这些中间神经元是如何被视觉输入控制的，并首次发现这些细胞在将感觉信息传递给新皮层时在做什么。我们的工作将在一定程度上解释为什么丘脑的紊乱，例如在衰老过程中，可能与认知能力下降有关，特别是在某些形式的血管性痴呆中。然而，这项研究的中心焦点是深入了解感觉信息是如何在看似简单的丘脑神经元回路中编码的。

The scientific communities' basic understanding of the brain is still too limited to offer any hope of comprehensively curing age-related cognitive decline and other common neurological disorders. To reach an adequate understanding of the basic mechanisms that control our brains, science is reliant on access to animal models that enable neuroscientists to study the cellular and molecular aspects of this most complex of organs. In this proposal, we aim to reach a greater understanding of how visual information is processed by our brains. Everything we see, hear and feel must pass through a relatively small part of our brain called the thalamus. We have known for several decades that a key role of the thalamus is to distribute salient features of our sensory world across the outer part of our brains called the neocortex to enable higher-order brain functions such as perception, cognition, generation of motor commands, spatial reasoning and language. Importantly, the thalamus stops relaying this sensory information to the neocortex when we are asleep. One of the most important steps in this process is the binding of a small inhibitory molecule called GABA (gamma amino butyric acid) to a type of membrane bound protein called the GABA-A receptor. The inhibitory neurotransmitter GABA is often released from local interneurons and high-resolution imaging studies from our laboratories have shown that thalamic interneurons are mainly found in a region of the thalamus called the dorsal lateral geniculate nucleus that receives sensory information from our eyes. We believe, therefore, that these interneurons have a specialised role to play in vision, but surprisingly we do not know what that role is. In most brain areas, the release of GABA is under the control of many distinct types of interneurons each doing slightly different jobs. For example, in the retina there are over 60 types of interneurons each responsible for converting the visual scene into electrical messages that are passed to the thalamus. Surprisingly, thalamic interneurons appear to be far less diverse, which rises the interesting question of how they may process the complex information arriving from the retina. To tackle this question, we first need to find out what type of visual information they are receiving. We have developed an innovative technique for doing this by using novel tracers that just label the inputs onto these thalamic interneurons. We now want to measure the electrical activity of these interneurons with specialized equipment that mimics how they would behave if they were receiving a visual stimulus. We are now in the unique position of being able to find out how these interneurons are controlled by visual input and discover for the first time what these cells are doing as they relay sensory information to the neocortex. Our work will go some way to explain why disturbances to the thalamus, for example during the ageing process, can be associated with cognitive decline especially during certain forms of vascular dementia. However, the central focus of this research is to reach a deeper understanding of how sensory information is encoded within the seemingly simple neuronal circuitry of the thalamus.