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

大脑中的神经细胞是如何应对温度变化的尚不清楚。神经细胞产生的电活动依赖于细胞膜上平衡的离子流动。正是这种平衡被温度严重改变，导致神经活动的失败，从而对活力造成严重后果。许多动物已经进化出补偿机制，使它们的大脑能够在更大的温度范围内工作。本研究通过研究几种不同甲壳类动物的相同神经细胞，以一种新颖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，而且可以识别，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高温和低温的先决条件。该项目将为各级学生提供识别温度对神经细胞生理学和前沿电生理学的影响的全面培训。结果将通过Youtube和各种公共宣传项目公开传播。当温度变化时，拥有维持重要神经元活动的补偿机制对动物的生存至关重要。最近来自甲壳类动物口胃神经系统中枢模式发生器的数据表明，下行投射神经元为运动网络提供外源性神经调节，可以抵消这些网络中的有害温度效应。补偿是通过平衡离子电导率的温度依赖性增加来实现的，允许对温度影响做出快速灵活的响应。下行投射神经元是许多类群运动回路的普遍组成部分，本项目的目的是验证通过神经调节进行的温度补偿是一种普遍存在且进化保守的假设。实验将在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上进行。具体来说，来自口胃神经节中已识别的调节和模式生成神经元的细胞外和细胞内记录，包括电压和动态箝位，将(1)确定具有相似耐温性的亲缘物种的温度补偿；(2)确定具有不同耐温性的远亲物种的温度补偿。这项研究将表明，神经调节不仅仅是增加神经系统灵活性的一种手段，因为它稳定了功能背景下的神经元活动。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.