AFFERENT REGULATION OF CHOLINERGIC FOREBRAIN NEURONS

胆碱能前脑神经元的传入调节

• 批准号: 6165407
• 负责人: LASZLO ZABORSZKY
• 金额: $ 26.26万
• 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/6165407
• 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)被组织起来调节分布在大脑中的神经元过程， 大脑皮层中的感觉、运动和高级认知系统。 药理学研究表明，多巴胺能和多巴胺能 刺激对皮层乙酰胆碱释放具有深远影响， 这表明这些传入神经在介导增加的 注意、唤醒和奖赏行为状态中的胆碱能紧张 机制等 拟议的实验将测试各种假设， 皮质胆碱能和相关的非胆碱能 特定基底前脑回路中的神经元受到 多巴胺能和多巴胺能传入。 将检验以下特定假设：1）前额叶 海马神经元轴突终末于不同类型的GABA能神经元， 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鉴定（即， 小清蛋白、钙结合蛋白D28、钙视网膜蛋白），收缩BF胆碱能 投射神经元 突触的数量和形态 胆碱能神经元将根据神经元的位置和/或类型而变化。 GABA能神经元 3)谷氨酸和多巴胺影响胆碱能 输出神经元通过不同的突触前和突触后机制。 为了实现这些目标，我们将进行结合解剖学和 电生理学研究 以下主要研究方向将是 （1）查明爆炸物的来源和爆炸地点; 基底前脑神经元上的多巴胺能和多巴胺能终末。 （二） 电生理特性的影响，刺激的 黑质或已确定BF上的推定的多巴胺能来源 神经元，在体内细胞外记录。 3)生物胞素的改造 标记的BF GABA能神经元，以鉴定它们与胆碱能神经元的突触。 神经元 4)多巴胺能和多巴胺能的细胞特征 受体。 这些研究将通过使用体内巨噬细胞 记录，传入通路的顺行追踪和双 免疫标记方法以各种组合在光和 电子显微镜水平，辅以计算机三维 重建已识别的神经元及其突触。