INTEGRETIVE INFLUENCES OF THALAMIC/CORTICAL INPUTS--PREFRONTAL CORTICAL FUNCTION

对精神分裂症病理生理学的研究支持了 多巴胺（DA）系统和前额叶皮层（PFC）之间的联系。 特别是，路易斯项目对精神分裂症的尸检研究， 提供的证据表明，这种疾病的特点可能是 减少PFC DA神经支配和丘脑皮质调节，这可能 最终影响信息处理的整合， 区域（科恩项目）。使用大鼠体内细胞内记录 模型，我们将研究涉及PFC活动的调节因素， 以及前额叶皮层如何调节皮层下多巴胺系统。更以 与Zigmond项目合作，我们将研究青春期前是否 PFC DA输入的中断改变了PFC输出神经元的调节 以及它们对中脑边缘DA系统的影响。这将使用体内 细胞内记录，以检查深层前边缘系统的生理学 PFC神经元在以下方面：1）前额叶对它们的调节 关联皮层输入和丘脑传入，以及这是如何 调制的DA，2）他们的相互作用与皮层下DA系统，和3） 青春期前与成人前额叶DA损伤的影响 皮层和丘脑对边缘前区神经元输入的调节 输出神经元每一项使用青春期前和成人病变的研究， 前额叶DA神经支配将与 由齐格蒙德计划进行的生化评估通过使用体内 电生理学方法，我们希望得到的信息，可以 与灵长类动物组织的生物物理学研究相结合（项目- Barrionuevo），这将与功能研究有关。 组织方案基金会（奥尔森项目）及其参与 精神分裂症的病理生理学

Studies into the pathophysiology of schizophrenia have support an association between the dopamine (DA) system and prefrontal cortex (PFC). In particular, postmortem studies of schizophrenia by Project-Lewis have provided evidence suggesting that this disorder may be characterized by a decrease in PFC DA innervation and thalamocortical regulation, which may ultimately impact on the integration of information processing in this region (Project-Cohen). Using in vivo intracellular recordings in a rat model, we will examine factors involved in the regulation of PFC activity, and how the PFC can modulate subcortical DA systems. Furthermore, in collaboration with Project-Zigmond we will examine whether prepubertal disruption of PFC DA inputs alters the regulation of PFC output neurons and their impact on mesolimbic DA systems. This will be done using in vivo intracellular recordings to examine the physiology of deep layer prelimbic PFC neurons in terms of the following: 1) their regulation by prefrontal associational cortical inputs and thalamic afferents, and how this is modulated by DA, 2) their interaction with subcortical DA systems, and 3) the influence of prepubertal versus adult lesions of the prefrontal DA innervation on the regulation of cortical and thalamic inputs to prelimbic output neurons. Each of the studies using prepubertal and adult lesions of the prefrontal DA innervation will be carried out in parallel with the biochemical assessments done by Project-Zigmond. By using an in vivo electrophysiological approach, we hope to derive information that can be integrated with the biophysical studies in primate tissue (Project- Barrionuevo) and that will be relevant to studies of the functional organization of the PFC (Project-Olson) and its involvement in the pathophysiology of schizophrenia.