Neuromodulation of a Rhythmic Network

节律网络的神经调节

• 批准号: 6794011
• 负责人: ANNE-ELISE TOBIN
• 金额: $ 2.65万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6794011
• 关键词: Hirudinea; brain regulatory center; computer simulation; heart rhythm; interneurons; membrane potentials; model design /development; neural conduction; neural information processing; neuromuscular transmission; neuropeptides; neurophysiology; neuroregulation; synapses; voltage /patch clamp

Most rhythmic motor patterns such as swimming, walking, chewing, and breathing are coordinated by neural networks called central pattern generators (CPGs). The ability of these networks to produce rhythmic output is determined by the membrane currents of the cells and the synaptic connections among the cells. Studies of a variety of vertebrate and invertebrate systems have shown that endogenous peptide modulators alter the output rhythm by modifying synaptic connections and/or membrane currents of neurons in the network (Dale and Kuenzi, 1997). Characterizing how modulators work aids our understanding of how rhythmic networks function and how they can respond adaptively to the environment by neuromodulation. This knowledge will advance understanding of CPG dysfunction, such as occurs in some respiratory and ambulatory disorders (Feldman and Gray, 2000; Feraboli-Lohnherr et al., 1999). Because of its small size and well-defined anatomy, the 14-interneuron network, controlling the leech heartbeat is a model system for exploring rhythmic network function. Within this network, two pairs of oscillator interneurons create the underlying alternating rhythm of the leech heartbeat. This proposal focuses on understanding how a neuromodulator acts on these oscillator interneurons to accelerate the heartbeat pattern. In addition, this proposal discusses the development of a computer model of these interneurons incorporating information about cell morphology to understand how morphology and ion channel distribution contribute to rhythmic activity. This series of experimental and modeling studies clarifies how neural networks produce rhythmic activity and how neuromodulation of current kinetics affects the rhythmic output.

大多数有节奏的运动模式，例如游泳，步行，咀嚼和呼吸，都由称为中央模式发生器（CPG）的神经网络协调。这些网络产生节奏输出的能力取决于细胞的膜电流和细胞之间的突触连接。 对多种脊椎动物和无脊椎动物系统的研究表明，内源性肽调节剂通过修改网络中神经元的突触连接和/或膜电流来改变输出节奏（Dale and Kuenzi，1997）。表征调节器的工作方式有助于我们对节奏网络的运作方式以及如何通过神经调节对环境适应环境的理解。 这些知识将提高对CpG功能障碍的理解，例如在某些呼吸系统疾病中发生（Feldman and Gray，2000； Feraboli-Lohnherr等，1999）。由于其尺寸较小且定义明确的解剖结构，控制水ech心跳是探索节奏网络功能的模型系统。 在这个网络中，两对振荡器中间神经元创建了水ech心跳的基础交替节奏。 该提议着重于理解神经调节剂如何在这些振荡器中间神经元上起作用以加速心跳模式。 此外，该建议还讨论了这些中间神经元的计算机模型的开发，该模型结合了有关细胞形态的信息，以了解形态和离子渠道分布如何有助于节奏活动。 这一系列的实验和建模研究阐明了神经网络如何产生节奏活性以及当前动力学的神经调节如何影响节奏输出。