Neurotransmitter Modulation of Neuronal Circuits

神经元回路的神经递质调节

• 批准号: 8968869
• 负责人: EVE E MARDER
• 金额: $ 40.47万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-12-01 至 2017-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8968869
• 关键词: Address; Agonist; Amines; Amino Acids; Antibodies; Attention; Behavior; Behavioral; Biological Neural Networks; Brain; Complement; Crustacea; Data; Dependence; Family; Family member; Fluorescent Dyes; Frequencies; Functional disorder; Funding; Ganglia; Gases; Grant; Individual; Locomotion; Mass Spectrum Analysis; Mental disorders; Methods; Moods; Nervous System Physiology; Nervous system structure; Neuromodulator; Neurons; Neuropeptides; Neurotransmitters; Pattern; Peptides; Physiological; Play; Property; Role; Sensory; Series; Signal Transduction; Sleep; Specific qualifier value; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Stomach; Synapses; System; Time; Variant; Work; biophysical properties; feeding; flexibility; member; nervous system disorder; neuronal circuitry; neuroregulation; operation; receptor; research study; response; voltage

DESCRIPTION (provided by applicant): All nervous systems employ a large umber of amines, amino acids and neuropeptides as neurotransmitters and neuromodulators. Despite years of work on individual brain signaling systems, the organizational principles underlying neuromodulation remain incompletely understood. The proposed work will employ the crustacean stomatogastric nervous system to address a series of general questions about neuromodulation of brain circuits. Mass spectrometry will be used to determine the identity of neuropeptides in specific sensory and modulatory neurons. The function of the specific neuropeptides found in identified neurons will be examined electrophysiologically. In cases in which multiple members of a peptide family are found in the same identified neurons, the potency and action of the different family members will be compared. To determine how a single neuron organizes receptors for 12 or 15 different neurotransmitters or modulators, neurons will be filled with fluorescent dye, and agonists applied to various regions of the neuron to localize its receptors. Further experiments will characterize the voltage-dependence and pharmacological profile of the evoked responses. The effects of neuromodulators on circuit reorganization will be studied with quantitative methods that determine how different frequency rhythms interact. Additionally, the effects of neuromodulators on signal propagation will be investigated by determining the extent to which externally imposed signals (sine waves of various frequencies) influence the activity of circuit neurons. Together these data will contribute to basic understandings of how different neuromodulatory systems can modify networks to produce behaviorally relevant changes in function.

描述（由申请人提供）：所有神经系统都采用大量胺，氨基酸和神经肽作为神经递质和神经调节剂。尽管在单个大脑信号系统上进行了多年的工作，但神经调节基础的组织原理仍未完全理解。拟议的工作将采用甲壳类突变神经系统来解决有关脑回路神经调节的一系列一般性问题。质谱法将用于确定特定感觉和调节神经元中神经肽的身份。在鉴定神经元中发现的特定神经肽的功能将在电生理上检查。如果在同一鉴定的神经元中发现了多个肽家族的多个成员，则将比较不同家族成员的效力和行动。为了确定单个神经元如何组织12或15个不同的神经递质或调节剂的受体，神经元将充满荧光染料，而激动剂应用于神经元的各个区域以定位其受体。进一步的实验将表征诱发反应的电压依赖性和药理特征。将使用定量方法来研究神经调节剂对电路重组的影响，以确定不同的频率节奏相互作用。此外，通过确定外部施加的信号（各种频率的正弦波）影响电路神经元的活性，将研究神经调节剂对信号传播的影响。这些数据共同有助于基本理解不同的神经调节系统如何修改网络以产生与行为相关的功能变化。