Regulation of Dorsal and Medial Raphe Neural Activity

背侧和内侧中缝神经活动的调节

• 批准号: 7424921
• 负责人: SHERYL G BECK
• 金额: $ 33.96万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7424921
• 关键词: Aggressive behavior; Anatomy; Animal Model; Animals; Anxiety; Area; Behavior; Behavioral; Brain; Characteristics; Corticotropin-Releasing Hormone Receptors; Dorsal; Emotional; Emotions; Engineering; Etiology; Exhibits; Foundations; Glutamates; Goals; Hormones; Immunohistochemistry; Knockout Mice; Location; Maps; Measures; Medial; Mediating; Mental Depression; Mental disorders; Mood Disorders; Mus; Neurons; Neurotransmitters; Phenotype; Physiology; Procedures; Property; Prosencephalon; Proteins; Rattus; Receptor Activation; Regulation; Research Personnel; Role; Serotonin; Serotonin Receptor 5-HT1A; Serotonin Receptor 5-HT1B; Site; Slice; Stress; Swimming; System; Techniques; Whole-Cell Recordings; clinically relevant; gamma-Aminobutyric Acid; nerve supply; neuronal cell body; novel; raphe nuclei; receptor; relating to nervous system; research study; response; therapy development

DESCRIPTION (provided by applicant): The cellular mechanisms underlying stress induced behaviors and the development and treatment of stress related psychiatric disorders most likely involve both the 5-HT cell body containing nuclei of the raphe as well as their projection areas in the limbic forebrain. The median (MR) and dorsal raphe (DR) are the principal sites where 5-HT cell bodies are located and they provide the majority of the 5-HT innervation of the forebrain. Approximately 50% of the neurons in the MR and DR are non-5-HT containing. The MR and DR projections terminate in many of the same limbic brain areas, but also have exclusive projections to other brain areas. The anatomy of the different subfields of the DR and within the MR is not the same. These distinctions have important implications in terms of regional selectivity of the subfields of the DR and the MR in controlling different emotional behaviors. The long term goal is to delineate both the common and disparate features of MR and DR cell neural activity. This information will provide a foundation for understanding the factors that differentially regulate 5-HT and non-5-HT physiology and may underlie some of the functional differences. The overall hypothesis is that there are discrete regional cellular differences in the 5-HT and non-5-HT containing neurons of the different subfields of the DR and MR. The excitatory neurotransmitter glutamate, the inhibitory neurotransmitter GABA and the stress hormone CRF are all posed to have selective and regionally distinct modulatory roles on DR and/or MR activity. In this application, the goal is to regionally map the differences in basic cellular characteristics (Specific Aim 1), excitatory glutamatergic (Specific Aim 2) and inhibitory GABAergic neural activity (Specific Aim 3) and their modulation by 5-HT1A, 5-HT1B, and CRF receptor activation. Selective alteration of these responses will be measured in 2 animal models, i.e., swim stressed rats and the 5-HT1B knockout mouse (Specific Aim 4). Whole cell recording techniques, immunohistochemistry, aRNA amplification and histological procedures will be used in the different subfields of the DR and MR in 5-HT and non-5-HT containing neurons. The clinical relevance of these studies is in supplying important information that will be crucial for understanding how the 5-HT neurotransmitter system regulates stress and emotions and how it may be involved in the etiology and treatment of mood disorders such as anxiety and depression.

描述（由申请人提供）：压力引起的行为的基础机制以及与压力相关的精神疾病的发展和治疗很可能涉及含有raphe核的5-HT细胞体及其在边缘前脑中的投影区域。中位数（MR）和背侧Raphe（DR）是位于5-HT细胞体的主要部位，它们提供了前脑5-HT神经的大部分。 MR和DR中约有50％的神经元含有非-5-HT。 MR和DR预测在许多相同的边缘大脑区域终止，但也对其他大脑区域进行了独家预测。 DR的不同子场的解剖结构和MR内的解剖学不是相同的。这些区别在控制不同情绪行为方面的区域选择性方面具有重要的含义。长期目标是描述MR和DR细胞神经活动的常见和不同特征。该信息将为理解差异调节5-HT和非5-HT生理的因素提供基础，并可能是一些功能差异的基础。总体假设是，在5-HT和非5-HT中包含DR和MR不同子场的神经元的区域细胞差异。兴奋性神经递质谷氨酸，抑制性神经递质GABA和应激激素CRF均被认为在DR和/或MR活性上具有选择性和区域不同的调节作用。在此应用中，目标是在区域绘制基本细胞特征（特定目标1），兴奋性谷氨酸能（特定目标2）和抑制性GABA能神经活动（特定的AIM 3）及其调节5-HT1A，5-HT1B的调节和CRF受体激活。这些反应的选择性改变将在2种动物模型，即游泳压力大鼠和5-HT1B敲除小鼠（特定的目标4）中进行测量。全细胞记录技术，免疫组织化学，ARNA扩增和组织学程序将在含有5-HT和非5-HT神经元的DR和MR的不同子场中使用。这些研究的临床相关性在于提供重要信息，这对于了解5-HT神经递质系统如何调节压力和情绪至关重要，以及如何参与焦虑和抑郁等情绪障碍的病因和治疗。