ANATOMY AND PHYSIOLOGY OF SUBSTANTIA NIGRA AFFERENTS

描述：(改编自申请者的摘要) 这项建议旨在描述 控制黑质多巴胺神经元活动的传入。 特别是，GABA能途径到多巴胺能的各个方面 起源于非多巴胺能质轴突侧支的神经元 将对黑质网状部投射神经元进行研究。中环 假说认为，多巴胺能神经元的许多重要输入 控制放电率和自发活动的过滤 网状部神经元。提出了六个具体目标。目标1.测试 认为存在生理功能的单突触的假设 黑质网状部GABA能投射之间的联系 黑质纹状体多巴胺能神经元和致密部 电生理手段。目的2.确定GABA的亚型 多巴胺能黑质纹状体神经元上的受体 新纹状体球区GABA能传入神经元的抑制作用 苍白球和黑质网状核的活体观察 神经药理学研究。目标3.确定相关影响 GABA-A和GABA-B突触传入对黑质纹状体放电模式的影响 活体中的神经元。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联系 神经元和黑质纹状体多巴胺能神经元的光和电子研究 电生理轴突侧支的显微分析 以网状部神经元为特征的细胞内或 细胞旁用生物细胞素标记。目标5.检验假设 GABA能网状部神经元轴突侧支和/或 苍白球的传入是抑制反应的主要原因 兴奋性刺激后致密部多巴胺能神经元 投入。目的6.检验个体纹状体和黑质 苍白球传入多巴胺能或非多巴胺能突触 黑质神经元的细胞内或细胞旁标记和 追踪轴突至黑质并进行双标记电子显微镜检查。

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.