AFFERENT REGULATION OF CHOLINERGIC FOREBRAIN NEURONS

胆碱能前脑神经元的传入调节

• 批准号: 6149063
• 负责人: LASZLO ZABORSZKY
• 金额: $ 5万
• 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 2002-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6149063
• 关键词: acetylcholine; afferent nerve; brain mapping; calretinin; cholinergic receptors; dopamine; dopamine receptor; electrophysiology; gamma aminobutyrate; glutamate receptor; glutamates; immunoelectron microscopy; laboratory rat; neural transmission; neuroanatomy; neurochemistry; prosencephalon; receptor expression

The goal of the proposed research is to understand how the basal foebrain (BF) is organized to modulate distributed neuronal processes within sensory, motor and higher order cognitive systems in the cerebral cortex. Pharmacological studies have shown that dopaminergic and glutamatergic stimulation have a profound effect on cortical acetylcholine release, suggesting a critical role for these afferents in mediating increased cholinergic tone in behavioral states of attention, arousal and reward mechanisms. The proposed experiments will test various hypotheses about the ways in which corticipetal cholinergic and associated non-cholinergic neurons in specific basal forebrain circuits are influenced by dopaminergic and glutamatergic afferents. The following specific hypothesis will be tested: 1) Prefrontal glutamatergic axons terminate on different type of GABAergic neurons in the basal forebrain. 2) Different types of BF GABAergic neurons, identified by the presence of different calcium binding proteins (i.e., parvalbumin, calbindin D28, calretinin), contract BF cholinergic projection neurons. The number of and topography of synapses on the cholinergic neurons will vary according to the location and/or the type of GABAergic neuron. 3) Glutamate and dopamine influence the cholinergic output neurons through different pre- and postsynaptic mechanisms. To accomplish these goals e will undertake on a combined anatomical and electrophysiological study. The following major lines of research will be pursued: 1) Identification of the sources and site of termination of dopaminergic and glutamatergic terminals on basal forebrain neurons. 2) Electrophysiological characterization of thee effect of the stimulation of the substantia nigra or putative glutamatergic sources on identified BF neurons, recorded extracellularly in vivo. 3) Reconstruction of biocytin labeled BF GABAergic neurons to identify their synapses with cholinergic neurons. 4) Cellular characterization of dopaminergic and glutamatergic receptors. These studies will be aided by using in vivo juxtacellular recording, anterograde tracing of afferent pathways and double immunolabeling methods in various combinations at both the light and electron microscopic level, supplemented by computerized 3-D reconstruction of identified neurons and their synapses.

拟议研究的目标是了解基底胎脑如何 (BF) 被组织来调节分布式神经元过程 大脑皮层的感觉、运动和高级认知系统。 药理学研究表明，多巴胺能和谷氨酸能 刺激对皮质乙酰胆碱的释放有深远的影响， 表明这些传入神经在调节增加的过程中发挥着关键作用 注意力、唤醒和奖励行为状态下的胆碱能张力 机制。 拟议的实验将测试有关的各种假设 皮质胆碱能和相关非胆碱能的方式 特定基底前脑回路中的神经元受到以下因素的影响 多巴胺能和谷氨酸能传入。 将检验以下具体假设：1）前额叶 谷氨酸能轴突终止于不同类型的 GABA 能神经元上 基底前脑。 2）不同类型的BF GABA能神经元， 通过不同钙结合蛋白的存在来识别（即， 小清蛋白、钙结合蛋白 D28、钙视网膜蛋白)、合同 BF 胆碱能 投射神经元。 突触的数量和地形 胆碱能神经元将根据位置和/或类型而变化 GABA能神经元。 3）谷氨酸和多巴胺影响胆碱能 通过不同的突触前和突触后机制输出神经元。 为了实现这些目标，我们将结合解剖学和 电生理学研究。 将开展以下主要研究方向 追求： 1) 查明终止的来源和地点 基底前脑神经元上的多巴胺能和谷氨酸能末端。 2） 刺激效应的电生理学特征 黑质或推定的 BF 上的谷氨酸来源 神经元，在体内细胞外记录。 3) 生物胞素的重建 标记 BF GABA 能神经元以识别其胆碱能突触 神经元。 4) 多巴胺能和谷氨酸能的细胞表征 受体。 这些研究将通过使用体内近细胞 记录、顺行追踪传入通路和双 光和光下各种组合的免疫标记方法 电子显微镜水平，辅以计算机 3-D 重建已识别的神经元及其突触。