Cortical pathways and synaptic mechanisms for texture discrimination learning in rodents

人类主要利用视觉系统来理解和诠释世界。因此，我们很难想象触摸世界的任何细节，也很难理解它的重要性。然而，如果我们不能根据物体的感觉来识别它们，我们肯定会认识到这种重要感觉所产生的丰富信息。当没有光线，我们在黑暗中摸索时，或者当我们在口袋或包里寻找我们看不见的东西时，触摸通常是最受欢迎的。消防员在烟雾弥漫的房间里探险时，依靠触觉；当外科医生戴上手术手套（这会改变触觉体验）时，他们需要重新学习如何感觉和抓住物体。在这些情况下，物体表面的小突起和凹陷的空间排列以及它们在时间上的屈服或偏移的方式，换句话说，表面的纹理，给了我们关于物体身份的大量信息。想象一下，你如何仅仅通过触摸来区分口袋里的旧（纸）和新（塑料）钞票。这项拨款旨在了解纹理信息是如何在大脑中处理的，以及大脑是如何适应和学习赋予特定纹理意义的。为此，我们将研究啮齿动物大脑的纹理处理。啮齿动物是夜行动物，因此高度依赖触觉信息来识别环境中的物体。啮齿动物是触觉专家。在实验室任务中，我们发现它们优先使用胡须来识别不同的纹理。啮齿类动物的鼻子两侧长着一排高度标准化的40根大胡须，它们可以前后移动（或摇动），有效地触诊和识别物体。值得注意的是，它们能够区分颗粒大小不同的表面，距离仅为18um，这一距离比面部胡须之间的间距小了几个数量级。我们可以教动物将奖励与特定的纹理联系起来，然后通过在探索过程中使大脑区域沉默来发现大脑的哪些区域参与其中。我们还可以记录来自相同大脑区域的神经元活动，并发现神经元如何在我们怀疑参与的那些地方编码纹理信息。到目前为止，对高阶触摸处理的研究通常倾向于在猴子身上进行。如果我们能够确定啮齿类动物的处理流的位置，就有可能在这个领域以更快的速度进行工作，并且可能需要更少的猴子进行研究。我们研究的第二个主要部分是关于当动物学习新的纹理或为熟悉的纹理赋予意义时，大脑是如何以及在哪里发生变化的。我们可以通过要求啮齿动物学习区分两种相似的纹理来获得奖励来测试这个想法。当他们学习的时候，我们可以想象大脑中神经元之间的突触连接。突触将神经元连接在一起，并允许它们彼此交流。具体来说，我们可以看到是否形成了新的连接，以及它们是否与纹理的记忆有关。为了做到这一点，我们可以在大脑中制造一个小窗口，通过产生GFP（绿色荧光蛋白）使感兴趣的神经元发出荧光。我们可以用双光子显微镜观察神经元上的树突棘（是突触的一半）。我们可以看到当动物学习时是否会产生新的树突棘。我们也可以使用分子探针选择性地渗透到新的刺上，来消除或抹去这些刺，看看新的刺是否确实是学习纹理辨别所必需的。这将帮助我们理解学习和记忆的物理基础。

Humans mainly use their visual system to understand and interpret the world. It is therefore often difficult for us to imagine the world of touch in any detail or understand its importance. Yet if we were unable to recognise objects that we pick up from the way they feel, we would surely recognise the wealth of information yielded up by this vital sense. Touch is most often appreciated when there is no light and we are feeling our way in the dark, or when we are looking for an object we cannot see in a pocket or a bag. Firefighters rely on their tactile sense when exploring smoke filled rooms; surgeons need to relearn how to feel and grasp objects when they wear surgical gloves (which alter the tactile experience). In these cases, the spatial arrangement of small protuberances and depressions on the surface of an object and the way they yield, or are deflected in time, in other words the texture of the surface, give us a great deal of information about the object's identity. Think of how you might distinguish an old (paper) and a new (plastic) note in your pocket purely by touch.This grant is aimed at understanding how texture information is processed in the brain and how the brain adapts and learns to attribute meaning to particular textures. To do this we will study texture processing in the rodent brain. Rodents are nocturnal animals and are therefore highly reliant on tactile information for identifying objects in their environment. Rodents are experts at touch. In laboratory tasks, we have found that they preferentially use their whiskers to identify different textures. Rodents have a highly stylised array of 40 large whiskers on either side of the snout that they can move back on forth (or whisk), effectively to palpate objects and recognise them. Remarkably, they are able to distinguish between surfaces that differ in particle size by just 18um, a distance that is orders of magnitude smaller than the spacing between whiskers on the face. We can teach the animals to associate a reward with a particular texture and then discover which areas of the brain are involved by silencing those brain areas during the exploration. We can also record neuronal activity from the same brain regions and discover how the neurones encode texture information in those places we suspect to be involved. So far, work on higher order touch processing has generally tended to be conducted in monkeys. If we could establish where the processing streams are located in rodents, there is a possibility that work would proceed at a faster pace in this field and fewer monkeys might need to be studied. The second major part of our study concerns how and where changes occur in the brain when animals learn about new textures or attribute meaning to familiar textures. We can test this idea by asking the rodents to learn to distinguish between two similar textures to acquire a reward. While they are learning, we can image the synaptic connections between neurones in the brain that might be involved. Synapses connect neurones together and allow them to communicate with one another. Specifically, we can see whether new connections are formed and whether they correlate with the memory of the texture. To do this we can make a small window in the brain and make the neurones of interest fluoresce by producing GFP (green fluorescent protein). We can view the dendritic spines (which are one half of the synapse) on the neurones using a 2-photon microscope. We can view whether new dendritic spines are produced when the animal learns. We can also eliminate or erase those spines using a molecular probe that selectively infiltrates new spines and see whether the new spines are indeed necessary for learning the texture discrimination. This will help us understand the physical basis of learning and memory in general.