Neuromodulation and Robustness of Neurons and Networks

项目摘要/摘要 这是一个请求，以整合三个正在进行的由NINDS资助的提案，这些提案 具有神经调节(R37 NS 17813)、温度补偿(R01 NS 81012)，以及 内在兴奋性的动态平衡调节的计算模型(项目#4 P01 NS07949)。这些项目共同构成了一种连贯的尝试，以了解 在以下情况下大脑回路的稳定性：a)广泛的神经调节，b)持续和快速 离子通道和受体的周转，以及c)退化和多重解决方案 单个神经元和电路水平。这些问题源于多年的计算和 甲壳类口胃神经节小回路的实验研究 (Stg)，但解决与所有神经系统相关的一般问题，从无脊椎动物 对人类来说。未来的实验将把实验和计算工作结合起来 了解神经元和网络中生物参数的相关性，从而 任何给定的参数都是可变的，而电路本身保持稳健性。动物到 将测量动物对扰动的反应变异性，所有 将测量STG回路中的突触，并调节多个 将研究单个神经元的神经调节剂受体。此外，自调整 将开发模型以找到一组神经元参数，使神经元能够 保持稳定，以应对干扰。这项工作将在一定程度上阐明 同样的动物也有可能产生类似的行为 不同的(退化)电路机制在不同的时间。如果是这样的话，这可以揭示 更大的电路可以如何在多个退化电路机制之间切换以 随着时间的推移产生稳定的行为。

Project Summary/Abstract This is a request to consolidate three ongoing NINDS-funded proposals that deal with neuromodulation (R37 NS 17813), temperature compensation (R01 NS 81012), and computational models of homeostatic regulation of intrinsic excitability (Project #4 of P01 NS07949). Together these projects comprise a coherent attempt to understand brain circuit stability in the face of: a) extensive neuromodulation, b) constant and rapid turnover of ion channels and receptors, and c) degenerate and multiple solutions at the single neuron and circuit level. These questions arise from years of computational and experimental work using the small circuits of the crustacean stomatogastric ganglion (STG), but address general problems relevant to all nervous systems, from invertebrates to humans. Future experiments will combine experimental and computational work to understand the correlations in biological parameters in neurons and networks that allow any given parameter to be variable while the circuit itself retains robustness. Animal to animal variability in response to perturbations will be measured, the strengths of all of the synapses in STG circuits will be measured, and the regulation of multiple neuromodulator receptors by single neurons will be studied. Additionally, self-tuning models will be developed to find sets of neuronal parameters that allow neurons to maintain stability in response to perturbations. This work will illuminate the extent to which the same animal can potentially generate similar behavior by substantially different (degenerate) circuit mechanisms at different times. If so, this can shed light on how larger circuits may switch between a number of degenerate circuit mechanisms to generate stable behaviors over time.