AFFERENT REGULATION OF CHOLINERGIC FOREBRAIN NEURONS

描述(申请人提供)：基底前脑(BF)是一个复杂的大脑区域，包含胆碱能和各种非胆碱能皮质顶叶神经元和中间神经元，在调节皮质活动方面发挥重要作用。皮质顶叶BF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有关。虽然胆碱能皮质顶叶成分得到了特别的重视，但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中的局部信息处理。在这个方案中，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)NPY中间神经元轴突侧支的局部靶点(S)是什么。3)局部含NPY神经元是否也接受前额叶传入。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，在光镜和电子显微镜水平上)将与电生理学(单细胞和脑电)技术相结合。在其他研究中，我们将以系统的方式研究网络水平的结构特征如何使基底前脑皮质顶叶系统参与协调联系和感觉运动功能。例如，我们将测试一种假设，即BF中投射到相互连接的躯体感觉(S1，S2)和运动皮质区域(M1)的神经元，以及在一些合成引导行为中相互协作的神经元，显示出比投射到邻近皮质区域的重叠更大的重叠，而邻近皮质区域反过来代表不连续的身体部位。在这些实验中，我们将使用双重逆行示踪剂注射到电生理鉴定的感觉或运动皮质表示，并将分析BF中逆行标记的胆碱能和非胆碱能神经元的分离或重叠。这些研究将对我们理解基底皮质网络中的信息处理产生重大影响，从而理解这些网络中的异常信息处理，这些异常信息处理是几种神经精神障碍的特征，包括阿尔茨海默病、精神分裂症和药物滥用。

DESCRIPTION (provided by applicant): 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 sensorimotor functions. For example, we will test the hypothesis that neurons in the BF which project to interconnected somatosensory (S1, S2) 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.