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（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神经元和中间神经元，在调节皮质活动中起重要作用。皮质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。虽然胆碱能皮质成分受到了特别的重视，但对皮质投射的非胆碱能成分知之甚少，特别是关于假定的谷氨酸能神经元和BF中的局部信息处理。在这个提议中，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中间神经元轴突侧枝的局部靶点是什么。3)局部含有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，原位杂交和解剖示踪，在光镜和电镜水平）将与电生理（单单元和脑电图）技术相结合。在进一步的研究中，我们将以系统的方式研究网络层面的结构特征如何使基底前脑皮质顶叶系统参与协调关联和感觉运动功能。例如，我们将测试BF中投射到相互连接的体感（S1, S2）和运动皮质区域（M1）的神经元的假设，这些神经元在一些知觉引导的行为中相互合作，比投射到相邻皮质区域的神经元表现出更大的重叠，而相邻皮质区域又代表不连续的身体部位。在这些实验中，我们将使用双逆行示踪剂注射到电生理学上识别的感觉或运动皮层表征中，并逆行标记BF中的胆碱能和非胆碱能神经元，以分析其分离或重叠。这些研究将对我们理解基底皮层网络中的信息处理产生重大影响，同时也将对理解这些网络中的异常信息处理具有一些神经精神疾病的特征，包括阿尔茨海默病、精神分裂症和药物滥用。