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: 10307082
• 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/10307082
• 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.

项目摘要/摘要 这是合并三项正在进行的Ninds资助的提案的请求 神经调节（R37 NS 17813），温度补偿（R01 NS 81012）和 内在兴奋性的体内稳态调节的计算模型（项目＃4的项目＃4 P01 NS07949）。这些项目共同构成了一致的尝试 面对以下方面的脑电路稳定性 离子通道和受体的营业额，以及c）在 单神经元和电路水平。这些问题来自多年的计算和 使用甲壳类气孔的小电路的实验性工作 （STG），但解决了与所有神经系统有关的一般问题，来自无脊椎动物 给人类。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学参数的相关性，以 当电路本身保留鲁棒性时，任何给定参数都是可变的。动物 将测量动物的变异性对扰动，所有的优势 将测量STG电路中的突触，并调节多个 将研究单个神经元的神经调节剂受体。另外，自我调整 将开发模型以找到允许神经元的神经元参数集 响应扰动而保持稳定性。这项工作将阐明 同一动物可以通过基本上可能产生相似的行为 在不同时间的不同（退化）电路机制。如果是这样，这可以揭示 较大的电路如何在许多退化电路机制之间切换到 随着时间的推移产生稳定的行为。