AFFERENT REGULATION OF CHOLINERGIC FOREBRAIN NEURONS

基底前脑是一个复杂的脑区，含有胆碱能和各种非胆碱能 皮质顶叶神经元和中间神经元在调节皮质活动中起着重要作用。皮质顶叶高炉 投射，特别是胆碱能成分，与记忆、注意力和许多 其他认知过程。虽然胆碱能皮质顶叶成分受到特别重视，但非常 对皮质顶叶投射的非胆碱能成分知之甚少，尤其是 推测的谷氨酸能神经元，以及BF内的局部信息处理。在本提案中，我们将 调查：1)BF的神经元亚型是否包括皮质投射的谷氨酸能 细胞，2)神经肽Y中间神经元轴突侧支的局部靶点(S)是什么。3)不管是不是本地的 含NPY的神经元也接受前额叶输入。在这些实验中，形态(单细胞 染色、免疫细胞化学标记、原位杂交和解剖示踪 (电子显微镜水平)将与电生理学(单个单元和脑电)技术相结合。在……里面 在其他研究中，我们将以系统的方式调查网络级别的架构特征 将使基底前脑皮质顶叶系统参与协调联想和感觉- 运动功能。例如，我们将测试BF中的神经元投射到 相互连接的躯体感觉(1美元，2美元)和运动皮质区域(M1)，并且相互协作 在一些合成引导的行为中，表现出比投射到邻近皮质区域更大的重叠 这反过来又代表了不连续的身体部位。在这些实验中，我们将使用双重逆行示踪剂 向电生理鉴定的感觉或运动皮质表征和逆行注射 将对BF中标记的胆碱能和非胆碱能神经元进行分离或重叠分析。这些 研究将对我们理解大脑基底皮质的信息处理产生重大影响 网络，以及随之而来的对这些网络中异常信息处理的理解 几种神经精神障碍的特征，包括阿尔茨海默病、精神分裂症和药物 虐待。

The basal forebrain (BF), a complex brain region that contains cholinergic and various non-cholinergic corticopetal neurons and interneurons, plays an important role in modulating cortical activity. Corticopetal BF projections, especially the cholinergic component, have been implicated in memory, attention, and many other cognitive processes. While the cholinergic corticopetal component received particular emphasis, very little is known about non-cholinergic components of the corticopetal projection, with special reference to putative glutamatergic neurons, and the local information processing in the BF. In this proposal we will investigate: 1) whether or not the neuronal subtypes of the BF include cortically projecting glutamatergic cells, 2) what the local target(s) of the axon collaterals of NPY interneurons are. 3) whether or not local NPY-containing neurons also receive prefrontal input. In these experiments morphological (single cell staining, immunocytochemical marking, in situ hybridization and anatomical tracing, both at the light and electron microscopical levels) will be combined with electrophysiological (single unit and EEG) techniques. In additional studies, we will investigate, in a systematic fashion, how architectural features at the network level would enable the basal forebrain corticopetal system to participate in coordinating association and sensory- motor functions. For example, we will test the hypothesis that neurons in the BF which project to interconnected somatosensory ($1, $2) and motor cortical areas (M1), and which cooperate with each other during somesthesis-guided behaviors, show larger overlap than projections to neighboring cortical areas that, in turn, represent non-contiguous body-parts. In these experiments, we will use dual retrograde tracer injections into electrophsyiologically identified sensory or motor cortical representations and retrogradely labeled cholinergic and non-cholinergic neurons in the BF will be analyzed for segregation or overlap. These studies will have significant impact on our understanding of information processing in basalo-cortical networks, and concomitantly the understanding of the aberrant information processing in these networks that characterize several neuropsychiatric disorders, including Alzheimer's disease, schizophrenia, and drug abuse.