AFFERENT REGULATION OF CHOLINERGIC FOREBRAIN NEURONS

胆碱能前脑神经元的传入调节

• 批准号: 6271687
• 负责人: LASZLO ZABORSZKY
• 金额: $ 3.8万
• 依托单位: RUTGERS THE STATE UNIV OF NJ NEWARK
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 1999-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6271687
• 关键词: afferent nerve; amines; calretinin; 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