AFFERENT REGULATION OF CHOLINERGIC FOREBRAIN NEURONS

胆碱能前脑神经元的传入调节

• 批准号: 6240290
• 负责人: LASZLO ZABORSZKY
• 金额: $ 2.51万
• 依托单位: RUTGERS THE STATE UNIV OF NJ NEWARK
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-01 至 1998-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6240290
• 关键词: afferent nerve; amines; cholinergic receptors; computer simulation; dorsal raphe nucleus; electron microscopy; immunocytochemistry; in situ hybridization; laboratory rat; light microscopy; nerve endings; neurons; neurotransmitters; prosencephalon; reticular formation; transneuronal degeneration

The long term goal of our research is twofold: 1) to understand the extent of how basal forebrain cholinergic neurons (BFC) are modulated by brainstem monoaminergic neurons and 2) to study whether the vulnerability of BFC neurons in neurodegenerative diseases could be related to the degeneration of monoaminergic input, or specific receptor composition of BFC neurons. To accomplish this goal we continue the anatomical and chemical characterization of monoaminergic afferents to specific subpopulations of BFC neurons. Specific attempt will be made to assess whether projections from the dorsal and median raphe nuclei, and the paramedian reticular formation terminate on BFC neurons. As a logical extension of these experiments we will identify the sources of afferents to local GABAergic (parvalbumin, calbindin and calretinin) and peptidergic (somatostatin and NPY) neurons and will study the relationship of these interneurons to BFC neurons. These studies will be aided by using in vivo and in vitro intracellular labeling techniques in combination with other tracing methods (PHA-L), and immunocytochemistry at both th light and electron microscopic level, supplemented by 3-D reconstruction of cholinergic neurons and their putative terminals. We will also characterize how the disruption of monoaminergic systems affects expression of monoaminergic receptors and neurotransmitter regulation in BFC neurons. In these experiments monoaminergic deprivation will be achieved by lesioning the individual monoaminergic cell groups or using various toxins (6-OHDA, 5, 6DHT, saporin-anti-DBH) and in situ hybridization technique will be used to measure changes in neurotransmitter enzyme (ChAT) or receptor (alpa2a, beta2, D1, D2 5HT1B) messages. 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, attention mechanisms or sensory processing, functions in which the BFC has been implicated. Moreover, our study may provide additional clues to the mechanism of monoaminergic/cholinergic interactions 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 disease.

我们研究的长期目标是双重的：1）了解程度 基础前脑胆碱能神经元（BFC）如何通过脑干调节 单胺能神经元和2）研究BFC的脆弱性是否 神经退行性疾病中的神经元可能与变性有关 单胺能输入或BFC神经元的特定受体组成。 为了实现这一目标，我们继续解剖学和化学 将单胺能传入的特征表征为特定亚群 BFC神经元。 将进行具体尝试来评估预测是否 从背和中间的raphe核以及秘书网状 地层终止于BFC神经元。作为这些的逻辑扩展 实验我们将确定局部gabaergic传入的来源 （Parvalbumin，calbindin和calretinin）和肽能 NPY）神经元，并将研究这些神经元与BFC的关系 神经元。 这些研究将通过使用体内和体外来帮助 细胞内标记技术与其他示踪方法结合 （PHA-L）和免疫细胞化学在TH光和电子显微镜下 水平，补充了胆碱能神经元的3-D重建及其 推定的终端。 我们还将表征单胺能系统的破坏 影响单胺能受体和神经递质的表达 BFC神经元的调节。 在这些实验中，单胺能剥夺 将通过将单个单胺能细胞组或 使用各种毒素（6-OHDA，5，6DHT，Saporin-Anti-DBH）和原位 杂交技术将用于测量神经递质的变化 酶（CHAT）或受体（Alpa2a，beta2，d1，d2 5ht1b）消息。 定义BFC的确切输入输出关系将提供 药理，行为或临床研究的必要数据库 旨在了解BFC在皮质激活中的特定作用， 注意机制或感觉处理，BFC具有的功能 被暗示。 此外，我们的研究可能会为 基底前脑中单胺能/胆碱能相互作用的机制。 这种互动在学习和记忆过程中也可能很重要， 他们的损失可能导致衰老和中的认知下降 痴呆疾病。