Reward, stress and hippocampal-prefrontal cortex circuitry

描述（由申请人提供）：厌恶应激损害前额皮质和海马体的可塑性和神经元结构。此外，压力和升高的糖皮质激素通过损害认知功能和增强焦虑，对与这些大脑区域相关的行为产生负面影响。最近的研究表明，积极或有益的压力可以通过促进神经元生长、增强认知功能和缓解焦虑来保护前额叶皮层和海马免受糖皮质激素升高的破坏性影响。虽然前额叶皮层和海马体是相互联系的，但我们对这些大脑区域在积极或消极压力下如何相互影响知之甚少。神经肽催产素可能在有益的社会情境下发挥保护作用，但其对海马体-前额叶皮层回路的影响尚不清楚。这一提议旨在探索海马体和前额叶皮层在环境条件下的相互作用，这些条件是有害的，而不是有益的。催产素在保护这些大脑区域免受潜在的破坏性荷尔蒙环境中的作用也将被探索。为了研究这些问题，我们将采用积极和消极的社会压力范式，特定大脑区域的暂时失活，催产素受体的操作，认知和焦虑行为分析以及结构可塑性的测量。这些研究的结果将告诉我们海马体和前额叶皮层在调节应激反应的积极和消极结果方面的相互作用。情绪障碍与认知功能障碍以及海马体和前额皮质体积减少有关。压力使人容易产生精神病理，包括抑郁和焦虑。了解海马体和前额叶皮层之间的相互作用，因为这些区域对经验作出反应，可能有助于开发有效的治疗方法，强调有利于改善认知功能和减少焦虑的生长促进机制。

DESCRIPTION (provided by applicant): Aversive stress impairs plasticity and neuronal architecture in both the prefrontal cortex and hippocampus. Moreover, stress and elevated glucocorticoids negatively impact behaviors associated with these brain regions, by impairing cognitive function and enhancing anxiety. Recent studies have shown that positive or rewarding stress protects the prefrontal cortex and hippocampus from the damaging effects of elevated glucocorticoids by promoting neuronal growth, enhancing cognitive function and relieving anxiety. Although the prefrontal cortex and hippocampus are interconnected, very little is known about how these brain regions influence one another under conditions of positive or negative stress. The neuropeptide oxytocin may play a protective role under rewarding social situations, but its influence over hippocampal-prefrontal cortex circuitry remains unexplored. This proposal is designed to explore interactions between the hippocampus and prefrontal cortex under environmental conditions that are detrimental compared to those that are beneficial. The role of oxytocin in protecting these brain regions from a potentially damaging hormonal milieu will also be explored. To investigate these issues, we will employ positive and negative social stress paradigms, temporary inactivation of specific brain regions, manipulations of oxytocin receptors, cognitive and anxiety behavioral assays and measures of structural plasticity. The results of these studies will inform us of the interplay between the hippocampus and prefrontal cortex in mediating positive and negative outcomes in response to stress. Mood disorders are associated with cognitive dysfunction and volumetric decreases in the hippocampus and prefrontal cortex. Stress predisposes individuals to develop psychopathology, including depression and anxiety. Understanding the interplay between the hippocampus and prefrontal cortex as these areas respond to experience may enable the development of effective therapies that emphasize growth-promoting mechanisms conducive to improved cognitive function and reduced anxiety. PUBLIC HEALTH RELEVANCE: This research is relevant to public health because it is focused on identifying mechanisms that protect the hippocampus and prefrontal cortex from the damaging effects of stress. Since the hippocampus and prefrontal cortex are dysfunctional in depression and anxiety disorders, this work may suggest targets for therapeutic interventions in mood disorders.