Temperature Compensation of Neuronal and Network Function

描述（由申请人提供）：温度是一种全局扰动，它或多或少地改变所有生物反应和过程。这一提议解决了一个基本问题，即当导致网络动力学的所有突触和内在特性都因温度而发生不同改变时，神经元回路如何在温度变化下保持稳健。为此，本文提出了对甲壳类动物中心模式生成网络——口胃神经节（STG）幽门节律的实验和计算研究。具体目的包括：研究温度对适应不同温度的动物幽门回路单个神经元和突触的影响；温度对适应不同温度动物STG神经元6种电压和时间依赖性膜电流影响的电压箝位表征温度对动态箝制STG神经元互抑回路的影响；基于电导的单神经元模型的发展并建立了pyloric网络模型，探讨了电路性能对温度变化的鲁棒性。这些数据将告知我们如何在个体之间保持稳健的电路性能，以及如何响应电路组件随时间的变化。这些实验将有助于我们理解具有不同基础电路组件的个体如何能够对许多环境扰动做出强有力的反应。此外，这些实验将深入了解高温可能导致癫痫发作和其他神经系统问题的机制。

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.