Neural coding and cellular dynamics

正是通过我们的感官，我们才能感知环境中发生的事情。第一批与外部世界接触的神经元表现出通才的行为：它们暴露在物理和化学刺激下，这些刺激包含了我们生存所需的所有信息，并进一步将这些信息转化为内部的“大脑表征”。他们的工作是进一步将这些信息传递给更多的专业神经元，这些神经元比其他神经元更专注于某些功能，例如刺激是否存在，是否正在增加，或者是否构成危险。*这项提议旨在揭示将外部刺激作为大脑输入转换为第一个神经元的数字输出，然后从这些转换到下一个神经元的输出的规则。结果将是对大脑内部语言的更深层次的理解，也就是我的长期目标--“神经密码”。除了对大脑代码进行这一关键的科学探索外，这项工作在实践中也很重要，有助于理解我们与环境的关系，并为增强大脑电路或在大脑电路出现故障时进行修复提供更有见地的指导。在接下来的五年里，我将培养5名本科生、5名硕士和6名博士。目标1通过检测被各种环境波动淹没的极其微小的刺激物，寻找许多动物达到超灵敏的规则。目标2通过揭示表示温度上升和下降的规则，重点研究大脑如何处理温度信息。当轴突周围的绝缘髓鞘随着时间的推移而变薄时，以及在某些疾病中，我们应对温度的能力就会受到影响，相关的希望是更好地了解温度是如何影响神经元的，并能够弥补这种损失。最后的目标3再次涉及编码和噪音，但提到了与认知有关的整个大脑节奏。通过观察不同尺度的神经编码，从单一的通才神经元到大型大脑回路，很可能更容易揭示大脑如何工作的一般规则，以及它使用的潜在语言。*这项工作本质上是理论和计算的。我们建立了预测数学模型，这些模型足够简单，可以用最少的生物成分来解释神经现象。这项工作将仔细利用现有的生物学数据，并受益于与实验神经生物学家的合作。该模型还用于通过理论分析或电子实验对功能进行预测，这些预测可以在新的实验中进行测试。这项研究将加深我们对大脑回路功能的认识。它还可能导致基于新发现的原理的新型传感技术(例如神经假体)，包括感应热量和电场的技术，或修复病理性大脑节律的技术。**

It is through our senses that we perceive what goes on in our environment. The first neurons in contact with the external world behave as generalists: they are exposed to physical and chemical stimuli that contain all the necessary information for our survival, and further convert that information into an internal "brain representation". Their job is further to pass on this information to more specialist neurons that focus on some features more than others, such as whether a stimulus is there or not, whether it is increasing, or poses a danger. ******This proposal aims to reveal the rules governing this conversion from external stimuli as brain inputs to the digital output of the first neurons, and then from these to the output of the next neurons. The result will be a deeper understanding on the internal language of the brain, i.e. of the "neural code", which is my LONG-TERM GOAL. Apart from pursuing this key scientific quest for the brain code, this work is important in practice to understand our relationship to the environment, and provide a more informed guide to enhancing brain circuitry or repairing it when it is faulty. ******For the next five years, I will train 5 undergraduates, 5 MSc and 6 PhD. Objective 1 seeks rules by which many animals achieve ultrasensitivity, detecting extraordinarily small stimuli that are swamped by environmental fluctuations of all kind. Objective 2 focuses on how the brain processes temperature information, by exposing the rules for representing increases and decreases in temperature. Our ability to deal with temperature is compromised when the insulating myelin sheath around axons thins away with the years, and in certain diseases, and the related hope is to better understand how temperature affects neurons in general and can compensate for such loss. The final Objective 3 deals again with coding and noise, but pushed up to the context of whole brain rhythms involved in cognition. By looking at neural coding at different scales, from single generalist neurons to large brain circuits, it is likely that general rules for how the brain does its work, and the underlying language it uses, can be more easily revealed. ******The work is theoretical and computational in nature. We formulate predictive mathematical models that are simple enough to explain neural phenomena with a minimal number of biological ingredients. The work will make careful use of existing biological data, and benefit from collaborations with experimental neurobiologists. The modelling also serves the purpose of making predictions about function - via theoretical analyses or in silico experiments - which can be tested in new experiments. This research will deepen our knowledge of brain circuit function. It may also lead to novel sensing technologies (e.g. neural prosthetics) based on newly found principles, including technologies to sense heat and electric fields, or to repair pathological brain rhythms. **