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

精神分裂症的病理生理学研究得到了支持和 多巴胺(DA)系统与前额叶皮质(PFC)的关系。 特别是，刘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征可能是 PFC DA神经支配和丘脑皮质调节减少，这可能 最终影响到信息处理的一体化在这个 地区(项目-科恩)。在大鼠体内使用细胞内记录 模型中，我们将研究参与调节PFC活性的因素， 以及PFC如何调节皮质下DA系统。此外，在 与齐格蒙德项目的合作我们将检查青春期前 中断PFC DA输入改变PFC输出神经元的调节 以及它们对中边缘DA系统的影响。这将通过在体内完成 用细胞内记录技术检测深层次的初步生理学 前额叶对PFC神经元的调节作用 联合皮质输入和丘脑传入，以及这是如何实现的 受DA调制，2)它们与皮质下DA系统的相互作用，3) 青春期前与成人对前额叶DA损害的影响 皮层和丘脑传入神经对初级刺激的调节作用 输出神经元。每项研究都使用了青春期前和成年期的皮损 前额多巴胺的神经支配将与 由齐格蒙德项目完成的生化评估。通过使用体内的 电生理学的方法，我们希望得到的信息可以 与灵长类组织的生物物理研究相结合(项目- Barrionuevo)，这将与功能的研究相关 PFC(项目-Olson)的组织及其参与 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.