AFFERENT REGULATION OF CHOLINERGIC FOREBRAIN NEURONS

我们研究的长期目标有两个：1)了解 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环路 2)了解跨神经元的基本机制。 BFC神经元与其传入神经元之间的相互作用。要做到这一点 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 将评估来自不同脑干的投射 单胺能核、中脑网状结构和来自 前额叶皮质终止于胆碱能前脑神经元。作为一名 这些实验的合乎逻辑的延伸我们将确定 局部GABA能和肽能神经元的传入 胆碱能神经元。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， 路西法·黄等)，以及各种不同的双重免疫标记方法 在光学和电子显微镜水平上的组合。 我们还将描述单胺能传入的中断 系统影响BFC和其他基础部位的神经递质调节 前脑神经元群。具体地说，我们将研究基因如何 单胺能和神经生长因子受体、神经递质酶的表达 (GAD、ChAT)和神经肽(NPY、生长抑素)是通过 去掉单胺能传入神经。更重要的是。我们将测试 单胺能后ChAT活性是否降低的假说 耗竭是通过前脑GABA能系统介导的 监测GABA能活动。 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在皮质激活或释放中的具体作用 与奖励相关的事件，与BFC有牵连的职能。 此外，我们的研究可能会提供更多的线索来解释 基底前脑的单胺能/胆碱能惰性反应。是这样的 交互作用在学习和记忆过程中也可能很重要，而且 它们的丢失可能是导致认知功能减退的原因之一 精神错乱的疾病。

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.