AFFERENT REGULATION OF CHOLINERGIC FOREBRAIN NEURONS

胆碱能前脑神经元的传入调节

• 批准号: 7051473
• 负责人: LASZLO ZABORSZKY
• 金额: $ 34.92万
• 依托单位: RUTGERS THE STATE UNIV OF NJ NEWARK
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-08-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7051473
• 关键词: acetylcholine; axon; calretinin; electroencephalography; electron microscopy; electrophysiology; glutamates; immunocytochemistry; in situ hybridization; interneurons; laboratory rat; neural transmission; neurons; neuropeptide Y; neuroregulation; prosencephalon; sensorimotor system

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.

描述（由申请人提供）：基础前脑（BF），这是一个复杂的大脑区域，其中包含胆碱能和各种非胆碱能皮质的神经元和中间神经元，在调节皮质活性中起着重要作用。皮质的BF投影，尤其是胆碱能成分，已与记忆，注意力和许多其他认知过程有关。虽然胆碱能皮质的成分特别强调了，但对皮质膜投射的非胆碱能成分知之甚少，特别是对假定的谷氨酸能神经元以及BF中的局部信息处理。在此提案中，我们将研究：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中间神经元的轴突侧支的局部靶标。 3）含有局部NPY的神经元是否也接受前额叶输入。在这些实验中，形态学（单细胞染色，免疫细胞化学标记，原位杂交和解剖学跟踪，在光和电子显微镜水平上）将与电生理学（单个单元和EEG）技术结合使用。在其他研究中，我们将以系统的方式调查网络级别的建筑特征如何使基础前脑皮质膜系统能够参与协调关联和感觉运动功能。例如，我们将检验以下假设：BF中的神经元互连的体感（S1，S2）和运动皮质区域（M1），并且在某些邻近的皮质区域中，在体外引导的行为中相互合作，在体外引导的行为中表现出更大的重叠。在这些实验中，我们将在BF中使用双重逆行示踪剂注射到电学鉴定的感觉或运动皮质表示，并在BF中分析逆行标记的胆碱能和非胆碱能神经元，以进行隔离或重叠。这些研究将对我们对底层网络中信息处理的理解产生重大影响，并同时了解这些网络中异常信息处理的理解，这些信息处理表征了几种神经精神疾病，包括阿尔茨海默氏病，精神分裂症和药物滥用。