Electrophysiology of the Prefrontal Cortex

前额皮质的电生理学

• 批准号: 7284551
• 负责人: PATRICIO O'DONNELL
• 金额: $ 20.96万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7284551
• 关键词: albino rat; brain metabolism; dopamine; dopamine receptor; electrophysiology; experimental brain lesion; glutamates; innervation; intermolecular interaction; membrane potentials; neural transmission; neuropathology; neurotransmitter agonist; neurotransmitter antagonist; neurotransmitter transport; prefrontal lobe /cortex; pyramidal cells; reinforcer; schizophrenia; tegmentum; tissue /cell preparation

DESCRIPTION (provided by applicant): The dopaminergic innervation of the prefrontal cortex is an important component of current hypotheses on the pathophysiology of schizophrenia. Unfortunately, the actions of dopamine in the cortex are not well understood, so we cannot envision a clear picture of how dopamine disturbances can result in symptoms. This field has a large number of inconsistent and often contradictory reports, with the actions of dopamine frequently characterized as inhibitory, excitatory or simply modulatory. We plan to test the hypothesis that dopamine in the prefrontal cortex sustains periods of depolarization (up states) during which synaptic activity is gated. The experiments will address: 1) whether dopamine cell activity is correlated with prefrontal cortical up states and whether inactivating the source of dopamine, the ventral tegmental area, eliminates or reduces up states; 2) whether dopamine cells and the prefrontal cortex enhance their synchrony in awake animals during conditions known to drive the dopaminergic projection; 3) whether dopamine can modulate plateau depolarizations resembling up states in a brain slice preparation; 4) whether activation of the mesocortical projection enhances metabolic activity in the prefrontal cortex; and 5) dopamine-glutamate interactions in prefrontal cortical slices obtained from animals with a neonatal ventral hippocampal lesion.

描述（申请人提供）：前额叶皮层多巴胺能神经支配是当前精神分裂症病理生理假说的重要组成部分。不幸的是，多巴胺在大脑皮层中的作用还没有被很好地理解，所以我们无法清楚地想象多巴胺干扰是如何导致症状的。这一领域有大量不一致且经常相互矛盾的报道，多巴胺的作用通常被描述为抑制性、兴奋性或简单的调节性。我们计划测试前额叶皮层中的多巴胺维持去极化期（向上状态）的假设，在此期间突触活动是门控的。该实验将探讨：1)多巴胺细胞活动是否与前额皮质上升状态相关，以及多巴胺来源腹侧被盖区失活是否消除或减少上升状态；2)在已知驱动多巴胺能投射的条件下，清醒动物的多巴胺细胞和前额皮质是否增强了它们的同步性；3)多巴胺是否可以调节脑切片准备过程中类似于上升状态的平台去极化；4)中皮层投射的激活是否会增强前额叶皮层的代谢活动；5)新生儿海马腹侧病变动物前额叶皮层多巴胺-谷氨酸相互作用切片。