Fatty Acids and Preclinical Models of Psychiatric Disorders

描述（由申请人提供）：饮食摄入缺乏omega-3多不饱和脂肪酸（n-3 PUFA）会对认知和情感功能产生负面影响。大量的精神病理学文献也暗示n-3 PUFA缺乏精神疾病，包括情绪障碍和精神分裂症。因此，考虑到现代饮食的趋势是减少n-3 PUFA摄入量，定义将n-3 PUFA水平与行为缺陷联系起来的潜在神经机制对基础神经科学以及公共卫生具有重要意义。这个探索性R21应用程序的总体目标是将一个与心理健康越来越相关的领域从现象学阶段推进到描绘大脑机制。我们建议使用啮齿动物模型来了解n-3 PUFA缺乏和补充对青春期大鼠前额叶皮层（PFC）和腹侧纹状体（vStr）协调神经元活动的影响机制。我们在n-3 PUFA缺乏的青春期大鼠中发现了细微的行为障碍，表明动机和注意力处理被破坏。在奖励驱动的学习任务中，将对行为参与的青春期大鼠的PFC亚区和vStr的单单位活动和局部场电位（LFPs）进行电生理记录，以解决两个假设：(1)n-3 PUFA缺乏会破坏PFC和腹侧纹状体对显著任务相关事件的神经元活动动态；(2)补充n-3 PUFA可以改善这些细胞破坏。预计这些研究结果将增加我们对影响n-3 PUFA缺乏和补充行为影响的功能回路的机制理解。

DESCRIPTION (provided by applicant): Deficiency in dietary intake of omega-3 polyunsaturated fatty acids (n-3 PUFA) negatively impacts cognitive and affective functioning. A plethora of psychopathology literature also implicates n-3 PUFA deficiency in psychiatric disorders, including mood disorders and schizophrenia. Thus, defining potential neuronal mechanisms that link n-3 PUFA levels to behavioral deficits has important implications for basic neuroscience, as well as for public health, given that the trend of the modern diet has been toward reduced n-3 PUFA intake. The overarching objective of this exploratory R21 application is to move a field, which is becoming increasingly relevant to mental health, forward from the phenomenological stage to delineating brain mechanisms. We propose to use a rodent model to gain mechanistic understanding of the impact of n-3 PUFA deficiency and supplementation on coordinated neuronal activity of the prefrontal cortex (PFC) and ventral striatum (vStr) of adolescent rats. We have found subtle behavioral impairments in n-3 PUFA deficient adolescent rats, suggestive of disrupted motivational and attentional processing. Electrophysiological recordings of single unit activity and local field potentials (LFPs) in PFC subregions and vStr of behaviorally engaged adolescent rats will be made during a reward driven learning task to address two hypotheses: (1) n-3 PUFA deficiency disrupts the dynamics of neuronal activity in the PFC and ventral striatum in response to salient task relevant events, (2) These cellular disruptions are ameliorated with n-3 PUFA supplementation. It is anticipated that the results of these studies will increase our mechanistic understanding of the functional circuitry that influences the behavioral effects of n-3 PUFA deficiency and supplementation. PUBLIC HEALTH RELEVANCE: Through the use of animal models and innovative methodology, this project will increase our mechanistic understanding of how omega -3 supplementation may serve as protective intervention in individuals with psychiatric disease vulnerability.