Electrophysiology of the Prefrontal Cortex

描述（由申请人提供）：前额皮质的多巴胺能神经支配是当前精神分裂症病理生理学假设的重要组成部分。不幸的是，多巴胺在皮质中的作用尚不清楚，因此我们无法清楚地了解多巴胺紊乱如何导致症状。该领域有大量不一致且常常相互矛盾的报告，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。我们计划测试这样的假设：前额皮质中的多巴胺维持去极化（向上状态）时期，在此期间突触活动被门控。实验将解决：1）多巴胺细胞活性是否与前额皮质向上状态相关，以及使多巴胺来源腹侧被盖区失活是否可以消除或减少向上状态； 2）在已知驱动多巴胺能投射的条件下，多巴胺细胞和前额皮质是否增强清醒动物的同步性； 3）多巴胺是否可以调节类似于脑切片制备中的向上状态的平台去极化； 4）中皮质投射的激活是否会增强前额皮质的代谢活动； 5）从患有新生儿腹侧海马病变的动物获得的前额皮质切片中的多巴胺-谷氨酸相互作用。

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.