Homeostatic Plasticity in A Neural Network: Conserved Output Via Variable Underlying Mechanisms

知识价值。同一类神经元在不同动物之间或同一动物内部的差异有多大？神经元必须如何精确地约束它们的许多膜电导值，才能在它们所在的网络中正常工作？利用计算机模型进行的理论研究认为，在单个神经元水平和网络水平上，相似的活动模式可以由相关的和补偿的膜和突触电流的不同组合产生。最近的研究为这一新观点增加了生物学证据：在不同动物的同一细胞中，膜电导水平和负责允许电流流过细胞膜的蛋白质（离子通道）的基因表达水平都有很大差异。这些结果表明，在不同动物的神经元中，存在不同的解决方案来执行相同的功能。本提案的第一个目标是研究导致这些不同解决方案的不同离子通道蛋白之间的功能关系。这将通过研究螃蟹（Cancer borealis）口胃神经节中多个离子通道基因同时在单个已鉴定神经元中的表达来实现。对这些表达模式的详细分析将确定单个细胞中通道表达和膜电流的关系。这些电导相互平衡和补偿的能力将通过计算（理论）和生物实验的结合进行测试，这些实验改变内源性膜电导并寻找其他电流的补偿。本建议的第二个目标是了解在面对急剧改变的输入时如何保持一致的网络输出的机制。口胃神经节的节律性活动依赖于神经系统其他中枢的下行输入。在这些输入被移除后，口胃神经节的活动很快就完全停止，但如果等待2-3天，节律就会恢复。这种恢复可能至少部分是离子通道表达改变的结果，离子通道的表达改变重新调整了这些网络以恢复功能输出。将进行实验来研究导致这种节律恢复的神经元特性的潜在变化。更广泛的影响。先前的研究表明，单个神经元使用组合的调谐规则来找到电导密度的组合，从而使它们在被发现的网络中具有足够的性能。这种自稳态可塑性最近已经成为一个越来越受关注的领域，因为它对神经系统各级神经网络的功能有影响。将本科生纳入概念和实验活动已经并将继续是舒尔茨博士专业努力的一个组成部分。

Intellectual Merit. How different are neurons of the same class across animals, or within a given animal? How precisely must neurons constrain the values of their many membrane conductances for them to function correctly in the networks in which they are found? Theoretical work using computer models has argued that similar activity patterns, both at the single neuron level and at the network level, can arise from different combinations of correlated and compensating membrane and synaptic currents. Recent work has added biological evidence for this novel idea: levels of both membrane conductance and the expression of genes responsible for the proteins which allow current to flow across the cell membrane (ion channels) vary considerably in the same cell in different animals. These results suggest that different solutions exist to carry out the same function in neurons from different animals. The first goal of this proposal is to investigate the functional relationships between different ion channel proteins that lead to these various solutions. This will be accomplished by studying the expression of multiple ion channel genes simultaneously in single identified neurons in the stomatogastric ganglion of the crab, Cancer borealis. A detailed analysis of these expression patterns will determine relationships of channel expression and membrane currents in single cells. The ability of these conductances to balance and compensate for one another then will be tested using a combination of computational (theoretical) and biological experiments that alter endogenous membrane conductances and look for compensation by other currents. The second goal of this proposal is to understand the mechanisms of how consistent network output is maintained in the face of radically altered inputs. The rhythmic activity of the stomatogastric ganglion is dependent on descending input from other centers of the nervous system. The activity of the stomatogastric ganglion activity stops completely soon after these inputs are removed, but if one waits 2-3 days the rhythm recovers. This recovery may at least in part be the result of changes in the expression of ion channels that re-tune these networks to regain functional output. Experiments will be performed to investigate the underlying changes in neuronal properties that lead to this recovery of rhythm. Broader Implications. Previous work suggests that individual neurons use a combination of tuning rules to find combinations of conductance densities that allow them adequate performance in the networks in which they are found. Such homeostatic plasticity recently has become an area of increased attention because it has implications for the function of neural networks at all levels of the nervous system. Incorporation of undergraduate students into the conceptual and experimental activities has been and will continue to be an integral part of Dr. Schulz' professional efforts.