Cortical pathways and synaptic mechanisms for texture discrimination learning in rodents

人类主要使用视觉系统来理解和解释世界。因此，我们常常很难想象触觉世界的任何细节，也很难理解它的重要性。然而，如果我们无法识别我们从物体的感觉中拾取的物体，我们肯定会认识到这种至关重要的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袋子里找不到的东西时，触摸最受欢迎。消防员在探索烟雾缭绕的房间时依靠触觉；外科医生需要重新学习戴上手术手套时如何感觉和抓住物体(这会改变触觉体验)。在这些情况下，物体表面的小凸起和凹陷的空间排列，以及它们在时间上产生或偏转的方式，换句话说，表面的纹理，给了我们关于物体身份的大量信息。想想你如何通过触摸来区分口袋里的旧钞票(纸币)和新钞票(塑料钞票)。这项资助旨在了解大脑是如何处理纹理信息的，以及大脑如何适应和学习将含义归因于特定的纹理。为了做到这一点，我们将研究啮齿动物大脑中的纹理处理。啮齿动物是夜间活动的动物，因此高度依赖触觉信息来识别其环境中的物体。啮齿动物是触摸方面的专家。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都有一排高度时髦的40根大胡须，它们可以向前移动(或拨动)，有效地触摸和识别物体。值得注意的是，他们能够区分颗粒大小仅相差18微米的表面，这个距离比面部胡须之间的间距小一个数量级。我们可以教动物将奖励与特定的质地联系起来，然后通过在探索过程中让这些脑区沉默来发现涉及到大脑的哪些区域。我们还可以记录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其中的地方编码纹理信息。到目前为止，关于高阶触摸加工的研究一般都是在猴子身上进行的。如果我们能确定啮齿动物的加工流在哪里，这一领域的工作就有可能进展得更快，需要研究的猴子可能会更少。我们研究的第二个主要部分涉及当动物学习新的纹理或将意义归因于熟悉的纹理时，大脑如何以及在哪里发生变化。我们可以通过让啮齿动物学会区分两种相似的纹理来测试这一想法，以获得奖励。当他们学习时，我们可以想象大脑中神经元之间可能参与的突触连接。突触将神经元连接在一起，并允许它们相互通信。具体地说，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相关。要做到这一点，我们可以在大脑中开一个小窗口，通过产生绿色荧光蛋白(GFP)来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(突触的一半)。我们可以观察到，当动物学习时，是否会产生新的树突。我们还可以使用分子探测器选择性地渗透新的脊椎来消除或消除这些脊椎，看看新的脊椎是否确实是学习纹理辨别所必需的。这将帮助我们从总体上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.