Temperature Compensation of Neuronal and Network Function

神经元和网络功能的温度补偿

• 批准号: 8418133
• 负责人: EVE E MARDER
• 金额: $ 35.08万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8418133
• 关键词: Address; Animals; Behavior; Biological; Biological Process; Brain Diseases; Cell physiology; Characteristics; Computer Simulation; Crabs; Crustacea; Data; Development; Etiology; Family; Febrile Convulsions; Financial compensation; Ganglia; Genetic; Goals; High temperature of physical object; Human; Individual; Individual Differences; Life Experience; Malignant Neoplasms; Measurement; Measures; Membrane; Modeling; Nervous System Physiology; Nervous system structure; Neurologic; Neurons; Neurosciences; Output; Pattern; Performance; Physiological; Population; Preparation; Process; Property; Reaction; Role; Seizures; Series; Solutions; Stereotyping; Synapses; Temperature; Testing; Theoretical Studies; Time; Variant; Work; base; computer studies; design; electrical property; extreme temperature; global environment; insight; network models; research study; response; synaptic function; voltage; voltage clamp

DESCRIPTION (provided by applicant): Temperature is a global perturbation that alters all biological reactions and processes to a greater or lesser degree. This proposal address the fundamental question of how neuronal circuits that underly behavior can be robust against temperature changes when all of the synaptic and intrinsic properties that give rise to network dynamics are altered differently by temperature. Towards this goal, experimental and computational studies of a crustacean central pattern generating network, the pyloric rhythm of the stomatogastric ganglion (STG) are proposed. Specific Aims include: studies of the effects of temperature on individual neurons and synapses of the pyloric circuit from animals acclimated to different temperatures; voltage-clamp characterization of the effects of temperature on six voltage and time-dependent membrane currents from STG neurons from animals acclimated to different temperatures; the effects of temperature on dynamic clamp constructed reciprocal inhibitory circuits made from pairs of isolated STG neurons; development of conductance-based single neuron models; and construction of pyloric network models to explore the robustness of circuit performance to altered temperature. These data will inform our understanding of how robust circuit performance is preserved across individuals and in response to alterations in the components of a circuit over time. These experiments will contribute to our understanding of how individuals with different sets of underlying circuit components can nonetheless respond robustly to many environmental perturbations. Additionally, these experiments will provide insight into the mechanisms by which high temperature may contribute to seizure and other neurological problems. PUBLIC HEALTH RELEVANCE: In humans, elevated temperatures can result in severe neurological and physiological problems, including among many, febrile seizures. The proposed work will illuminate the mechanisms by which elevated temperature can result in disordered brain activity, and is important for understanding why different individuals in the natural population respond differently to many global environmental insults.

描述（由申请人提供）：温度是一种全球扰动，它或多或少地改变了所有生物反应和过程。该提案解决了一个基本问题，即当所有引起网络动力学的突触和内在特性因温度而改变的所有突触和固有特性时，基本行为的神经元电路如何稳健地变化。为了实现这一目标，提出了对甲壳类中央模式产生网络的实验和计算研究，该目标是气孔神经节（STG）的幽门节奏。具体目的包括：对温度对幽门电路的单个神经元和突触的影响，从适应于不同温度的动物的幽门电路；电压钳表征温度对适应于不同温度的动物的STG神经元的六个电压和时间依赖的膜电流的影响；温度对由成对孤立的STG神经元制成的互惠抑制回路的动态夹具的影响；开发基于电导的单神经元模型；并构建幽门网络模型，以探索电路性能对变化的鲁棒性。这些数据将使我们了解如何在个人之间保持稳健的电路性能以及随着时间的流逝的组件的变化。这些实验将有助于我们理解具有不同基础电路组件集合的个体如何对许多环境扰动的反应。此外，这些实验将洞悉高温可能导致癫痫发作和其他神经系统问题的机制。 公共卫生相关性：在人类中，温度升高可能会导致严重的神经系统和生理问题，包括许多高热癫痫发作。拟议的工作将阐明温度升高会导致大脑活动障碍的机制，并且对于理解为什么自然人群中的不同个体对许多全球环境侮辱的反应不同。