Neuromodulation and Robustness of Neurons and Networks

神经元和网络的神经调节和鲁棒性

• 批准号: 10059279
• 负责人: EVE E MARDER
• 金额: $ 96.04万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10059279
• 关键词: Address; Animals; Behavior; Biological; Brain; Computer Models; Crustacea; Financial compensation; Funding; Future; Ganglia; Goals; Human; Individual; Invertebrates; Ion Channel; Light; Measures; Membrane Proteins; Modeling; National Institute of Neurological Disorders and Stroke; Nervous system structure; Neuromodulator Receptors; Neurons; Regulation; Synapses; Temperature; Time; Work; experimental study; flexibility; neuroregulation; receptor; response

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.

项目概要/摘要 这是一项合并三项正在进行的 NINDS 资助提案的请求，这些提案涉及 具有神经调节 (R37 NS 17813)、温度补偿 (R01 NS 81012) 和 内在兴奋性稳态调节的计算模型（项目#4 P01 NS07949）。这些项目共同构成了一个连贯的尝试来理解 面对以下情况时脑回路的稳定性：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) 简并和多重溶液 单个神经元和电路级别。这些问题源于多年的计算和 使用甲壳动物口胃神经节小电路的实验工作 （STG），但解决与无脊椎动物的所有神经系统相关的一般问题 对人类。未来的实验将结合实验和计算工作 了解神经元和网络中生物参数的相关性，从而允许 任何给定的参数都是可变的，而电路本身保持鲁棒性。动物至 将测量动物对扰动反应的变异性，所有动物的优势 STG 电路中的突触将被测量，并调节多个 将研究单个神经元的神经调节受体。另外，自调整 将开发模型来寻找神经元参数集，使神经元能够 保持稳定以应对扰动。这项工作将阐明 同一动物可能会产生类似的行为 不同时间的不同（简并）电路机制。如果是这样，这可以阐明 更大的电路如何在多种简并电路机制之间切换 随着时间的推移产生稳定的行为。