Extrinsic neuromodulation is a general mechanism to stabilize neural network function during temperature changes

大脑中的神经细胞如何处理温度变化还不清楚。神经细胞产生的电活动依赖于穿过细胞膜的平衡离子流。正是这种平衡被温度严重改变，导致神经活动失败，从而对生命力造成严重后果。许多动物已经进化出补偿机制，使它们的大脑能够在更宽的温度范围内发挥作用。这项研究通过研究几种不同甲壳动物中的相同神经细胞，以一种新的方法阐明了这种进化保守机制。甲壳类动物是解决这些问题的理想系统，因为它们的神经细胞很大，而且它们生活在各种温度下。认识到进化上保守的温度补偿机制不仅对于理解动物如何在不断变化的环境中生存至关重要，而且最终也是研究和治疗体温过高和过低的先决条件。该项目将为各级学生提供识别温度对神经细胞生理学和尖端电生理学影响的综合培训。调查结果将通过Youtube和各种公共外联方案公开传播。当温度变化时，具有维持重要神经元活动的补偿机制对动物生存至关重要。最近的数据显示，从中央模式发生器在甲壳类动物口胃神经系统的下行投射神经元，提供外在的神经调节运动网络可以抵消不利的温度影响，在这些网络。通过平衡离子电导随温度的增加来实现补偿，从而对温度影响做出快速灵活的响应。下行投射神经元是许多分类群的运动回路中的通用构建块，并且该项目的目标是测试以下假设：通过神经调节进行温度补偿是一种普遍现象并且在进化上是保守的。将对几种具有不同进化背景和温度耐受性的近亲和远亲甲壳类动物进行实验。具体而言，来自口胃神经节中所识别的调节和模式生成神经元的细胞外和细胞内记录（包括电压钳和动态钳）将（1）确定具有相似温度耐受性的相关物种中的温度补偿，以及（2）确定具有不同温度耐受性的远亲物种中的温度补偿。这项研究将表明，神经调节不仅仅是一种增加神经系统灵活性的手段，因为它在功能背景下稳定神经元活动。该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估来支持。

How nerve cells in the brain deal with temperature changes is not well understood. The electrical activity that nerve cells produce rely on a well-balanced flow of ions across the cell membrane. It is this balance that is critically altered by temperature, leading to failures in neural activity and accordingly severe consequences for vitality. Many animals have evolved compensatory mechanisms allowing their brains to function over a wider temperature range. This research elucidates such evolutionary conserved mechanisms with a novel approach by studying the same nerve cells in several different species of crustaceans. Crustaceans are ideal systems to address these issues because of their large and identified nerve cells and they live at a variety of temperatures. Recognizing evolutionarily conserved mechanisms for temperature compensation is not only crucial for understanding how animals survive in continuously changing environments, they are ultimately also a prerequisite for the investigation and treatment of hyper- and hypothermia. This project will provide comprehensive training in identifying temperature effects on nerve cell physiology and in cutting-edge electrophysiology for all levels of students. Results will be disseminated publicly through Youtube and a variety of public outreach programs. Possessing compensatory mechanisms that maintain vital neuronal activity when temperature changes is critical for animal survival. Recent data from central pattern generators in the crustacean stomatogastric nervous system have shown that descending projection neurons that provide extrinsic neuromodulation to motor networks can counterbalance detrimental temperature effects in these networks. Compensation is achieved by counterbalancing temperature-dependent increases of ionic conductances, allowing for a quick and flexible response to temperature influences. Descending projection neurons are universal building blocks in the motor circuits of many taxa, and the goal of this project is to test the hypothesis that temperature compensation via neuromodulation is a widespread phenomenon and evolutionarily conserved. Experiments will be carried out on several closely and distantly related crustaceans with various evolutionary backgrounds and temperature tolerances. Specifically, extra- and intracellular recordings, including voltage- and dynamic clamp, from identified modulatory and pattern generating neurons in the stomatogastric ganglion will (1) determine temperature compensation in related species with similar temperature tolerance and (2) determine temperature compensation in distantly related species with different temperature tolerance. This study will show that neuromodulation is more than a means to increase flexibility in the nervous system in that it stabilizes neuronal activity in a functional context.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.