Fatty Acids and Preclinical Models of Psychiatric Disorders

描述(由申请人提供)：膳食中omega-3多不饱和脂肪酸(n-3多不饱和脂肪酸)摄入量不足对认知和情感功能产生负面影响。过多的精神病理学文献还表明，n-3多不饱和脂肪酸缺乏与精神障碍有关，包括情绪障碍和精神分裂症。因此，鉴于现代饮食的趋势是减少n-3PUFA的摄入量，确定将n-3PUFA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健康具有重要意义。这一探索性的R21应用的首要目标是将一个与精神健康日益相关的领域从现象学阶段向前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多不饱和脂肪酸缺乏和补充对青春期大鼠前额叶皮质(PFC)和腹侧纹状体(VSTR)协调神经元活动的影响。我们在n-3多不饱和脂肪酸缺乏的青春期大鼠中发现了微妙的行为障碍，提示动机和注意力加工中断。在奖励驱动的学习任务中，将记录行为参与的青春期大鼠PFC亚区和VSTR中的单个单位活动和局部场电位(LFP)，以解决两个假设：(1)n-3PUFA缺乏扰乱了PFC和腹侧纹状体神经元活动的动力学，以响应显著的任务相关事件，(2)补充n-3PUFA可改善这些细胞破坏。预计这些研究的结果将增加我们对影响n-3多不饱和脂肪酸缺乏和补充的行为效应的功能回路的机制的理解。

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.