AFFERENT REGULATION OF CHOLINERGIC FOREBRAIN NEURONS

胆碱能前脑神经元的传入调节

• 批准号: 3408060
• 负责人: LASZLO ZABORSZKY
• 金额: $ 17.42万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-08-01 至 1994-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3408060
• 关键词: acetylcholine; afferent nerve; brain mapping; brain stem; central neural pathway /tract; choline acetyltransferase; cholinergic receptors; gamma aminobutyrate; glutamate decarboxylase; growth factor receptors; immunoelectron microscopy; laboratory rat; neural information processing; neural transmission; neuropeptide Y; neuropeptide receptor; neurotrophic factors; prosencephalon; receptor expression; somatostatin

The long term goal of our research is twofold 1) to understand how basal forebrain cholinergic neurons (BFC) together with other local non-cholinergic neurons participate in specific basal forebrain circuits and 2) to understand the fundamental mechanisms of transneuronal interactions between BFC neurons and their afferents. To achieve this goal, we will continue the anatomical and chemical characterization of afferents to specific subpopulations of BFC neurons. Specific attempts will be made to assess whether projections from different brainstem monoaminergic nuclei, the midbrain reticular formation and from the prefrontal cortex terminate on cholinergic forebrain neurons. As a logical extension of these experiments we will identify the sources of afferents to local GABAergic and peptidergic neurons which are connected with the cholinergic neurons. These studies will be aided by using in vivo and in vitro (anterograde and retrograde) tracer techniques (PHA-L, Lucifer Yellow, etc), and double immunolabeling methods in various combinations at both the light and electron microscopic level. We will also characterize how the disruption of monoaminergic afferent systems affects neurotransmitter regulation in the BFC and other basal forebrain neuronal populations. Specifically, we will study how gene expression for monoaminergic and NGF receptors, neurotransmitter enzymes (GAD, ChAT) and neuropeptides (NPY, somatostatin) is regulated through removal of monoaminergic afferents. Furthermore. we will test the hypothesis whether the decrease of ChAT activity after monoaminergic depletion Is mediated through the forebrain GABAergic system by monitoring GABAergic activity. Defining the precise Input-output relations of the BFC will provide the necessary database for pharmacological, behavioral or clinical studies designed to understand the specific role of BFC in cortical activation or reward related events, functions in which the BFC has been implicated. Moreover, our study may provide additional clues to the mechanism of monoaminergic/cholinergic inerteractions in the basal forebrain. Such interactions may also be important in learning and memory processes, and their loss may contribute to the cognitive decline seen in aging and in dementing diseases.

我们研究的长期目标是双重的：1）了解基础 前脑胆碱能神经元（BFC）与其他局部 非胆碱能神经元参与特定的基底前脑回路 2）了解跨神经元的基本机制 BFC神经元与其传入神经之间的相互作用。实现这一 目标，我们将继续解剖和化学表征 BFC神经元的特定亚群的传入。 具体尝试 将评估是否从不同的脑干投射 单胺能核，中脑网状结构和从 前额叶皮质终止于胆碱能前脑神经元。 作为 这些实验的逻辑延伸，我们将确定的来源， 局部GABA能和肽能神经元的传入， 与胆碱能神经元有关。 这些研究将通过使用 体内和体外（顺行和逆行）示踪技术（PHA-L， 荧光黄等），以及各种免疫标记方法中的双重免疫标记方法。 在光和电子显微镜水平的组合。 我们还将描述单胺能传入神经的中断 系统影响BFC和其他基础神经递质的调节 前脑神经元群体。 具体来说，我们将研究基因如何 单胺能和NGF受体、神经递质酶的表达 (GAD，ChAT）和神经肽（NPY，生长抑素）通过以下途径调节： 去除单胺能传入神经。 此外。我们将测试 假设ChAT活性的降低是否在单胺能 消耗通过前脑GABA能系统介导， 监测GABA能活性。 确定BFC的精确投入产出关系将提供 药理学、行为学或临床研究的必要数据库 旨在了解BFC在皮质激活中的具体作用， 奖励相关事件，BFC参与的功能。 此外，我们的研究可能会提供更多的线索， 基底前脑单胺能/胆碱能相互作用。 等 相互作用在学习和记忆过程中也很重要， 他们的损失可能会导致认知能力的下降， 精神错乱的疾病