DOPAMINERGIC MODULATION OF NUCLEUS ACCUMBENS AFF

最近关于精神分裂症病因学的理论发生了转变 他们的关注点从多巴胺能系统的初级病理学转向 皮质系统的作用及其潜在的病理调节 伏隔核内的多巴胺能传递。为了这个 原因，这个项目将研究原子核内的相互作用 伏隔是兴奋性和多巴胺能传入中的一种 结构。这些实验将表征调制的 大脑皮质兴奋性传入通过汇聚兴奋性传入 海马体和杏仁体，并进一步研究这些影响 伏隔核的传入受到多巴胺的调节。的影响 腹侧投射细胞终末释放的多巴胺 将被盖区与外源性应用的效果进行比较 为了研究多巴胺能神经元的定位水平 调制。最后，多巴胺的影响将在 多巴胺受体亚型术语与选择性的使用 对抗者。研究将首先在活体细胞外进行 电生理学，以便为申请人提供技术 电生理学方面的技能，以及确定 皮层和边缘的兴奋性传入和多巴胺能传入 伏隔核神经元的动作电位。然后，研究将搬到 活体细胞内电生理学以检测这些 突触水平上的相互作用。这些研究将描述突触的特征 的病理变化可能导致更改的事件 与精神分裂症相关的新皮质和颞叶。

Recent theories regarding the etiology of schizophrenia have shifted their focus from primary pathology in dopaminergic systems to focus on the role of cortical systems and their potential pathological modulation of dopaminergic transmission within the nucleus accumbens. For this reason, this project will examine the interactions within the nucleus accumbens among the excitatory and dopaminergic afferents to this structure. The experiments will characterize the modulation of neocortical excitatory afferents by converging excitatory inputs from the hippocampus and amygdala, and further examine how the influences of these afferents in the accumbens are modulated by dopamine. The effect of dopamine released from the terminals of cells projecting from the ventral tegmental area will be compared with effects of exogenously applied dopamine in order to study the level of localization of dopaminergic modulation. Finally, the effects of dopamine will be further defined in terms of dopamine receptor sub-types with the use of selective antagonists. Studies will first be conducted using in vivo extracellular electrophysiology, in order to provide the applicant with technical skills in electrophysiology and to determine the interactive effects of cortical and limbic excitatory afferents and dopaminergic afferents on action potentials in accumbens neurons. Studies will then move into in vivo intracellular electrophysiology in order to examine these interactions at a synaptic level. The studies will characterize synaptic events that may be altered as a result of pathological changes in the neocortex and temporal lobe associated with schizophrenia.