Reward, stress and hippocampal-prefrontal cortex circuitry

描述（由申请人提供）：厌恶性压力损害前额叶皮层和海马的可塑性和神经元结构。此外，压力和糖皮质激素升高会通过损害认知功能和增强焦虑来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，积极的或有益的压力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皮质和海马免受糖皮质激素升高的破坏性影响。虽然前额皮质和海马体是相互联系的，但人们对这些大脑区域在积极或消极压力条件下如何相互影响知之甚少。神经肽催产素可能在奖励性的社会情境中发挥保护作用，但其对大脑前额叶皮层回路的影响尚未被探索。这个提议的目的是探索海马和前额皮质之间的相互作用的环境条件下，是有害的，而不是那些是有益的。催产素在保护这些大脑区域免受潜在的有害激素环境的影响方面的作用也将被探索。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，特定脑区的暂时失活，催产素受体的操纵，认知和焦虑行为测定和结构可塑性的措施。这些研究的结果将告诉我们，海马体和前额叶皮层之间的相互作用，在调解积极和消极的结果，以应对压力。 情绪障碍与认知功能障碍和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学，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。 公共卫生相关性：这项研究与公共卫生有关，因为它的重点是确定保护海马体和前额叶皮层免受压力破坏性影响的机制。由于抑郁症和焦虑症患者的海马体和前额皮质功能障碍，这项工作可能会为情绪障碍的治疗干预提供目标。

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.