AFFERENT REGULATION OF CHOLINERGIC FOREBRAIN NEURONS

我们研究的长期目标有两个：1)了解 脑干对基底前脑胆碱能神经元的调节 单胺能神经元和2)研究BFC易损性 神经退行性疾病中的神经元可能与退行性疾病有关 单胺能输入，或BFC神经元的特定受体组成。 为了实现这个目标，我们继续进行解剖和化学研究 特定亚群的单胺能传入神经的特征 BFC神经元。将进行具体尝试，以评估预测 中缝背核、中缝正中核和旁正中网状核 形成终止于BFC神经元。作为这些功能的逻辑扩展 实验中，我们将确定局部GABA能的传入来源 (小白蛋白、钙结合蛋白和钙视黄素)和多肽能(生长抑素和 并将研究这些中间神经元与BFC的关系 神经元。这些研究将通过在体内和体外使用来辅助 结合其他示踪方法的细胞内标记技术 (PHA-L)，光镜和电子显微镜下的免疫细胞化学 水平，辅以胆碱能神经元的三维重建及其 可能是终点站。 我们还将描述单胺系统的破坏是如何 影响单胺类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 将通过损毁单个单胺能细胞群或 使用各种毒素(6-OHDA、5，6DHT、皂苷-抗胸腺激素)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，D25HT1b)消息。 定义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， 注意机制或感觉处理，BFC具有的功能 被牵连了。此外，我们的研究可能会为 基底前脑单胺能/胆碱能相互作用的机制。 这种交互作用在学习和记忆过程中也可能很重要， 而它们的丢失可能是导致认知能力下降的原因之一 痴呆症。

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.