ANATOMY AND PHYSIOLOGY OF SUBSTANTIA NIGRA AFFERENTS

黑质传入神经的解剖学和生理学

• 批准号: 6151601
• 负责人: James M Tepper
• 金额: $ 19.66万
• 依托单位: RUTGERS THE STATE UNIV OF NJ NEWARK
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-02-01 至 2002-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6151601
• 关键词: GABA receptor; afferent nerve; biocytin; brain electrical activity; dopamine receptor; excitatory aminoacid; laboratory rat; lenticular nucleus; neuroanatomy; neurons; neurophysiology; substantia nigra; tissue /cell culture

DESCRIPTION: (Adapted from the applicant's abstract) The experiments in this proposal are designed to describe the anatomy and physiology of afferents that control the activity of substantia nigra dopamine neurons. In particular, various aspects of a GABAergic pathway to dopaminergic neurons originating from the axon collaterals of non-dopaminergic substantia nigra pars reticulata projection neurons will be studied. The central hypothesis is that many of the important inputs to dopaminergic neurons that control the rate of firing and spontaneous activity are filtered through pars reticulata neurons. Six specific aims are proposed. Aim 1. To test the hypothesis that there is a physiologically functional monosynaptic connection between substantia nigra pars reticulata GABAergic projections neurons and pars compacta nigrostriatal dopaminergic neurons with electrophysiological means. Aim 2. To determine the subtype of the GABA receptor on the dopaminergic nigrostriatal neuron that mediates the inhibitory influence of GABAergic afferents arising from neostriatum, globus pallidus and substantia nigra par reticulata with in vivo neuropharmacological studies. Aim 3. To determine the relative influences of GABA-A and GABA-B synaptic inputs on the firing pattern of nigrostriatal neurons in vivo. Aim 4. To look for anatomical evidence of a direct monosynaptic connection between substantia nigra pars reticulata projection neurons and nigrostriatal dopaminergic neurons by light and electron microscopic analysis of the axon collaterals of electrophysiologically characterized pars reticulata neurons that were intracellularly or juxtacellularly labeled with biocytin. Aim 5. To test the hypothesis that activation of GABAergic pars reticulata neuron axon collaterals and/or pallidonigral inputs are responsible for the inhibitory responses seen in pars compacta dopaminergic neurons after stimulation of presumed excitatory inputs. Aim 6. To test the hypothesis that individual striatonigral and pallidonigral afferents synapse with either dopaminergic or non-dopaminergic neurons in substantia nigra by intracellular or juxtacellular labeling and tracing axons to nigra and performing double label electron microscopy.

描述：（改编自申请人的摘要）实验 该提案旨在描述的解剖学和生理学 控制黑质多巴胺神经元活动的传入神经。 特别是，GABA能途径的多巴胺能途径的各个方面 起源于非多巴胺能质轴突侧支的神经元 将研究黑质网状部投射神经元。 中央 假设是多巴胺能神经元的许多重要输入 控制发射率和自发活动通过过滤 网状部神经元。 提出了六项具体目标。 目标 1. 测试 假设存在具有生理功能的单突触 黑质网状部 GABA 能投影之间的联系 神经元和黑质纹状体致密部多巴胺能神经元 电生理手段。 目标 2. 确定 GABA 的亚型 多巴胺能黑质纹状体神经元上的受体，介导 来自新纹状体、球状体的 GABA 能传入的抑制影响 苍白球和黑质网状结构与体内 神经药理学研究。 目标 3. 确定相对影响 GABA-A 和 GABA-B 突触输入对黑质纹状体放电模式的影响 体内的神经元。 目标 4. 寻找直接的解剖学证据 黑质网状部投射之间的单突触连接 光和电子神经元和黑质纹状体多巴胺能神经元 电生理学轴突侧枝的显微分析 表征了细胞内或细胞内的网状部神经元 用生物胞素进行近细胞标记。 目标 5. 检验以下假设： GABA能网状部神经元轴突侧支的激活和/或 苍白球黑质输入负责抑制反应 刺激假定的兴奋性后致密部多巴胺能神经元 输入。 目标 6. 检验个体纹状体黑质和 苍白质黑体传入突触具有多巴胺能或非多巴胺能 通过细胞内或细胞旁标记来识别黑质中的神经元 追踪轴突至黑质并进行双标记电子显微镜检查。