Neural coding and cellular dynamics

正是通过我们的感官，我们感知环境中发生的事情。与外部世界接触的第一批神经元表现得像通才：它们暴露在包含我们生存所需的所有必要信息的物理和化学刺激下，并进一步将这些信息转化为内部的“大脑表征”。它们的工作是进一步将这些信息传递给更专业的神经元，这些神经元比其他神经元更专注于某些特征，比如刺激是否存在，是否在增加，或者是否构成危险。这一建议旨在揭示从外部刺激作为大脑输入到第一个神经元的数字输出，然后从这些到下一个神经元的输出，这种转换的规则。结果将是对大脑的内部语言，即“神经代码”有更深的理解，这是我的长期目标。除了对大脑密码进行关键的科学探索外，这项工作在实践中对理解我们与环境的关系很重要，并为增强大脑回路或在故障时修复它提供更明智的指导。未来五年，我将培养5名本科生，5名硕士，6名博士。目标1寻找许多动物获得超灵敏度的规则，它们能探测到被各种环境波动淹没的非常小的刺激。目标2通过揭示表示温度升高和降低的规则，重点关注大脑如何处理温度信息。当轴突周围的绝缘髓鞘随着年龄的增长而变薄时，以及在某些疾病中，我们处理温度的能力就会受到损害，相关的希望是更好地理解温度是如何影响神经元的，并能弥补这种损失。最后的目标3再次涉及编码和噪声，但将其推到了涉及认知的全脑节律的背景下。通过观察不同尺度的神经编码，从单一的通才神经元到大的大脑回路，很可能可以更容易地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性和计算性的。我们制定的预测数学模型足够简单，可以用最少数量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。该模型还可以通过理论分析或计算机实验对功能进行预测，这些预测可以在新的实验中进行验证。这项研究将加深我们对脑回路功能的认识。它还可能导致基于新发现原理的新型传感技术（例如神经假肢），包括感应热和电场的技术，或修复病理脑节律的技术。

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.