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

平衡资源和能量的使用以获得神经系统的最佳性能

• 批准号: BB/K01854X/1
• 负责人: Bruce Graham
• 金额: $ 30.57万
• 依托单位: University of Stirling
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FK01854X%2F1
• 关键词: Balancing; resource; energy; usage; optimal

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.

大脑的可塑性是最大的科学挑战之一，并且由于其对于大脑能够自我修复或通过适当的神经疗法和假体被借给“帮助之手”的含义而在一般社区中引起了极大的兴趣（参见例如Norman Doidge的畅销书“The Brain that Changes Itself”，Penguin 2007）。我们的工作将提供一个集中的，但希望有意义的新见解的过程中，大脑可以调整自己，以适应不断变化的环境。我们将使用计算机模拟的数学模型建立从实验数据来探索哺乳动物听觉系统的早期阶段的操作。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“信息”的操作要求，在环境中的声音，编码的耳蜗核神经元的活动。大脑是一个复杂而动态的信息处理系统，由大量但有限的噪声组件（细胞和相关的细胞外和细胞内信号系统）组成，必须以节能的方式运行。我们将检验这样一个假设，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该脑区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，这可能与传入听觉信息的最佳处理相冲突。该项目对大脑内在可塑性的理解将最终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引起内在的神经可塑性机制，这可能会增强甚至阻碍治疗。这里特别感兴趣的是人工耳蜗植入的发展，以治疗传统助听器无法补偿的听力受损。这些植入物产生电信号以响应声音并刺激听觉神经（最常见）或耳蜗核。已经用其信号仅具有完整耳蜗的分辨率和动态范围的一小部分的植入物实现了显著的结果（Wilson & Dorman（2008）Coplanar implants：Current designs and future possibilities，Journal of Rehabilitation 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，但人工耳蜗植入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：“耳蜗植入物作为一个系统工作，其中所有部分都很重要，包括麦克风，处理策略，经皮链接，接收器/刺激器，植入电极，植入耳蜗的功能解剖结构和用户的大脑。其中，迄今为止，大脑在植入物设计中受到的关注最少。“我们的工作将提供有关脑干听觉系统内在可塑性影响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”方法来研究神经系统。这有两个方面：（1）对神经功能采取整体观点，包括活动依赖性调节，噪音和能量消耗等方面，以及（2）紧密集成的实验和计算建模计划。人们熟悉计算机在天气预报和气候变化预测中的应用，但对计算机在计算生物学和神经科学中的应用的认识较少。适当地传播我们的工作可以让我们了解计算机和实验如何共同提供对神经系统详细工作的洞察。

项目成果

Activity-dependent regulation decreases metabolic cost in the auditory brainstem

活动依赖性调节降低听觉脑干的代谢成本

• DOI: 10.1109/ner.2015.7146622
• 发表时间: 2015
• 作者: Michel C

Phase changes in neuronal postsynaptic spiking due to short term plasticity.

• DOI: 10.1371/journal.pcbi.1005634
• 发表时间: 2017-09
• 期刊: PLoS computational biology
• 影响因子: 4.3
• 作者: McDonnell MD;Graham BP
• 通讯作者: Graham BP

Computational modelling predicts activity-dependent neuronal regulation by nitric oxide increases metabolic pathway activity

计算模型预测一氧化氮的活动依赖性神经元调节会增加代谢途径活动

• DOI: 10.1186/1471-2202-16-s1-p84
• 发表时间: 2015
• 期刊: BMC Neuroscience
• 影响因子: 2.4
• 作者: Michel C

Identification and modelling of fast and slow Ih current components in vestibular ganglion neurons.

• DOI: 10.1111/ejn.13021
• 发表时间: 2015-11
• 期刊: The European journal of neuroscience
• 作者: Michel CB;Azevedo Coste C;Desmadryl G;Puel JL;Bourien J;Graham BP
• 通讯作者: Graham BP

Nitric oxide activity-dependent regulator compensates synaptic depression and enhances metabolic efficiency in the auditory brainstem

• DOI: 10.1186/1471-2202-15-s1-p154
• 发表时间: 2014-07-21
• 期刊: BMC Neuroscience
• 影响因子: 2.4
• 作者: Michel CB;Hennig MH;Graham BP
• 通讯作者: Graham BP