Functional Consequences of Modulation of CPG Feedback to Descending Projection Neurons

CPG 反馈调节对下降投射神经元的功能影响

• 批准号: 1051189
• 负责人: Dawn Blitz
• 金额: $ 35万
• 依托单位: University of Pennsylvania
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2011-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1051189&HistoricalAwards=false
• 关键词: Functional; Consequences; Modulation; CPG; Feedback

The neural circuits, called central pattern generators (CPGs), underlying rhythmic behaviors (e.g., walking, breathing, chewing) are functionally flexible, producing multiple versions of a particular behavior (e.g., walking, running, swimming). A central goal in neuroscience is to determine how the output of a behaviorally-appropriate circuit is selected from such multifunctional circuits. Projection neurons are a major source for altering circuit output and, like most neural circuits, CPG circuits provide feedback to their projection neuron inputs. However, little is known regarding the function and modifiability of this feedback. Thus, this proposal aims to determine whether the strength of CPG feedback to projection neurons is modifiable and, if so, how such modulation alters projection neuron activity and the resulting CPG output pattern. To this end, multiple electrophysiological techniques will be utilized at the level of the projection neuron, CPG and muscle. It is anticipated that this project will provide the first demonstration of long-term modulation of CPG feedback and a cellular-level analysis of its functional consequences. It will also emphasize the under-appreciated concept that neural systems do not operate via a unidirectional flow of information, but require bidirectional communication between so called hierarchical levels. Both general principles and specific circuit mechanisms determined in the crustacean stomatogastric nervous system used in this proposal have effectively translated to other systems, including the mammalian CNS. The demonstration that circuit feedback is modifiable would open a new line of research in other systems, where feedback was not previously considered as a site of plasticity in determining CPG output. This project will provide training opportunities for graduate and undergraduate students, comprising cellular- to systems-level experimentation and analysis, including comprehensive training in electrophysiology, an experimental area in which women and other groups are particularly underrepresented. Students will have opportunities to present their work and interact with colleagues at local, national and international meetings each year.

神经回路，称为中枢模式发生器（CPG），潜在的节律行为（例如行走、呼吸、咀嚼）在功能上是灵活的，可以产生特定行为的多个版本（例如行走、跑步、游泳）。神经科学的一个中心目标是确定如何从此类多功能电路中选择行为适当的电路的输出。投射神经元是改变电路输出的主要来源，并且与大多数神经电路一样，CPG 电路为其投射神经元输入提供反馈。然而，人们对这种反馈的功能和可修改性知之甚少。因此，该提案旨在确定投射神经元的 CPG 反馈强度是否可修改，如果可以，这种调制如何改变投射神经元活动以及由此产生的 CPG 输出模式。为此，将在投射神经元、CPG 和肌肉水平上利用多种电生理学技术。预计该项目将首次演示 CPG 反馈的长期调节及其功能后果的细胞水平分析。它还将强调一个未被充分认识的概念，即神经系统不是通过单向信息流进行操作，而是需要所谓的层次级别之间的双向通信。本提案中使用的甲壳动物口胃神经系统中确定的一般原理和具体电路机制已有效地转化为其他系统，包括哺乳动物中枢神经系统。电路反馈可修改的演示将为其他系统开辟一条新的研究路线，在这些系统中，反馈以前并不被认为是确定 CPG 输出的可塑性场所。该项目将为研究生和本科生提供培训机会，包括细胞级到系统级的实验和分析，包括电生理学的综合培训，这是一个女性和其他群体代表性特别不足的实验领域。每年，学生将有机会在当地、国家和国际会议上展示他们的作品并与同事互动。