ANATOMY AND PHYSIOLOGY OF SUBSTANTIA NIGRA AFFERENTS

描述：（改编自申请人的摘要） 本提案旨在描述 控制黑质多巴胺神经元活动的传入神经。 具体地，本文描述了GABA能途径至多巴胺能途径的各个方面。 起源于非多巴胺能实质轴突侧支的神经元 将研究黑质网状部投射神经元。 中央 一种假说认为，多巴胺能神经元的许多重要输入， 控制发射率和自发活动被过滤通过 网状部神经元 提出了六个具体目标。 目标1. 测试 假设存在生理功能性单突触 黑质网状部GABA能投射之间的联系 神经元和黑质纹状体多巴胺能神经元 电生理手段。 目标2. 为了确定GABA的亚型 多巴胺能黑质纹状体神经元上的受体，介导 来自球状体新纹状体GABA能传入的抑制作用 苍白球和网状黑质 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 体内神经元 目标4。 去寻找一种直接的 黑质网状部投射间的单突触联系 黑质纹状体多巴胺能神经元 电生理轴突侧支的显微分析 特征性的网状部神经元， 用生物胞素标记的细胞间质。 目标5。 为了验证这个假设， 激活GABA能网状部神经元轴突侧支和/或 苍白球黑质的输入负责抑制反应， 多巴胺能神经元刺激后，假定兴奋性 输入。 目标6。 为了检验个体纹状体黑质和 苍白球黑质传入神经与多巴胺能或非多巴胺能神经突触 黑质神经元的细胞内或细胞外标记， 追踪轴突到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.