Balancing resource and energy usage for optimal performance in a neural system

大脑的可塑性是最大的科学挑战之一，并引起了广大社区的极大兴趣，因为它意味着大脑能够自我修复，或通过适当的神经疗法和假体得到“帮助”(例如，参见诺曼·多伊奇的畅销书“改变自己的大脑”，企鹅出版社，2007年)。我们的工作将为大脑适应不断变化的环境的过程提供一个集中但有意义的新见解。我们将使用计算机模拟根据实验数据建立的数学模型来探索哺乳动物听觉系统的早期运作。我们将研究这个大脑区域如何动态地配置自己，以满足传入的关于环境中声音的“信息”的操作需求，这些信息由耳蜗核中的神经元活动编码。大脑是一个复杂而动态的信息处理系统，它由大量但有限的噪声组件(细胞以及相关的细胞外和细胞内信号系统)组成，必须以高效的方式运行。我们将测试这一假设，即特定的可塑性机制根据神经元处理高频或低频声音的不同而对大脑区域的神经元进行不同的调节。此外，我们假设可塑性也试图最大限度地减少神经元使用的能量，这可能与对传入的听觉信息的最佳处理相冲突。通过这个项目增加对大脑内在可塑性的理解，最终将对神经疗法的发展产生影响。神经功能障碍的治疗不可避免地会调用内在的神经可塑性机制，这些机制可能会加强甚至阻碍治疗。这里特别令人感兴趣的是人工耳蜗的开发，用于治疗传统助听器无法弥补的听力受损。这些植入物对声音产生电信号，并刺激听神经(最常见的)或耳蜗核。其信号分辨率和动态范围仅为完整人工耳蜗的一小部分的植入物已经取得了显著的效果(Wilson&Dorman(2008)Cochlear Implants：Current Designments and Future Possitions，Journal of Recoveration Research&Development 45：695-730)。这完全归功于大脑的适应能力。尽管取得了这一成功，但人工耳蜗术的改进将通过对植入物刺激所引发的内在可塑性机制的更好理解来实现。引用Wilson&Dorman(2008)的话说：“人工耳蜗是一个系统，其中所有部分都很重要，包括麦克风、处理策略、经皮连接、接收器/刺激器、植入的电极、植入耳蜗的功能解剖以及使用者的大脑。其中，大脑是迄今为止植入物设计中最不受关注的。”我们的工作将提供关于脑干听觉系统内在可塑性含义的机制和理论的数据。这个项目需要提高公众意识的另一个方面是我们使用“系统”的方法来研究神经系统。这有两个方面：(1)从整体上看待神经功能，包括依赖活动的调节、噪音和能源消耗等方面；(2)实验和计算模型的紧密结合方案。人们熟悉计算机在天气预报和气候变化预测中的应用，但对其在计算生物学和神经科学中的应用知之甚少。适当地传播我们的工作可以提供一个快照，说明计算机和实验如何一起提供对神经系统详细工作的洞察。

The plasticity of the brain is one of the great scientific challenges and is of enormous interest in the general community because of the implications it has for the brain being able to repair itself, or be lent "a helping hand" by appropriate neural therapies and prostheses (see for example the popular book, "The Brain that Changes Itself" by Norman Doidge, Penguin 2007). Our work will provide a focussed, but hopefully significant new insight into the processes by which the brain can adjust itself to changing circumstances.We will use computer simulations of mathematical models built from experimental data to explore the operation of an early stage of the mammalian auditory system. We will study how this brain region dynamically configures itself to meet the operational demands of incoming 'information' about sounds in the environment, encoded by the activity of neurons in the cochlear nucleus. The brain is a complex and dynamic information processing system that is built from a large, but finite set of noisy components (cells and associated extracellular and intracellular signalling systems) and must operate in an energy efficient way. We will test the hypothesis that specific plasticity mechanisms adjust neurons in this brain region differently depending on whether they are processing high or low frequency sounds. Further, we postulate that plasticity is also trying to minimise the energy used by the neurons, and that this might be in conflict with the optimum processing of incoming auditory information.The increased understanding of the brain's intrinsic plasticity resulting from this project will ultimately have implications for the development of neural therapies. Treatments for neural dysfunction inevitably invoke intrinsic neural plasticity mechanisms that might enhance or even hinder the treatment. Of specific interest here is the development of cochlear implants to treat impaired hearing that cannot be compensated for by conventional hearing aids. These implants generate electrical signals in response to sounds and stimulate either the auditory nerve (most commonly) or the cochlear nucleus. Remarkable results have already been achieved with implants whose signals have only a fraction of the resolution and dynamic range of an intact cochlear (Wilson & Dorman (2008) Cochlear implants: Current designs and future possibilities, Journal of Rehabilitation Research & Development 45:695-730). This is entirely due to the brain's ability to adapt. Despite this success, improvements in cochlear implants will come through an improved understanding of the intrinsic plasticity mechanisms that are being invoked by the implant's stimulation. To quote from Wilson & Dorman (2008): "Cochlear implants work as a system, in which all parts are important, including the microphone, the processing strategy, the transcutaneous link, the receiver/stimulator, the implanted electrodes, the functional anatomy of the implanted cochlea, and the user's brain. Among these, the brain has received the least attention in implant designs to date." Our work will provide data on the mechanisms and theories of the implications of intrinsic plasticity in the brainstem auditory system. A further aspect of this project that needs increased public awareness is our use of a "systems" approach to studying a neural system. This has two aspects: (1) taking a holistic view of neural function that includes aspects such as activity-dependent regulation, noise and energy consumption, and (2) a tightly integrated programme of experiments and computational modelling. People are familiar with the use of computers in weather forecasting and climate change predictions, but there is less awareness of their use in computational biology and neuroscience. Appropriate dissemination of our work can give a snapshot of how computers and experiments together can provide insight into the detailed workings of the nervous system.