高情绪反应性与糖皮质激素受体调节的分子不同的海马杏仁核回路的激活有关

IF 4.3 2区 医学 Q1 NEUROSCIENCES
Qiang Wei , Vivek Kumar , Shannon Moore, Fei Li, Geoffrey G. Murphy, Stanley J. Watson , Huda Akil
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引用次数: 0

摘要

情绪的特征不仅在于它们的价态,还在于它们是稳定的还是不稳定的。然而,我们不了解控制情绪反应动态性质的分子或电路机制。我们已经表明,前脑中的糖皮质激素受体过度表达(GRov)会导致高度反应性小鼠焦虑行为增加,情绪反应波动更大。这种表型在发育早期就形成了,并一直持续到成年。然而,介导这种终生情绪不稳定的神经回路仍然未知。在本研究中,GRov小鼠腹侧齿状回(vDG)的光遗传学刺激导致焦虑行为的范围更大,持续时间更长。cFos表达分析表明,GRov小鼠对vDG激活的放大行为反应与特定脑区神经元活性的增加有关。与野生型小鼠相比,GRov小鼠在腹侧CA1(vCA1)表现出谷氨酸能/GABA能激活失衡,并选择性增加基底后杏仁核复合体的谷氨酸能激活。此外,前脑GR过表达导致海马和后基底外侧杏仁核(pBLA)内神经元的分子不同亚群的激活增加,这从vCA1中的钙结合蛋白1+谷氨酸能神经元和pBLA中的DARPP-32/Pp1r1b+谷氨酸能神经元中的cFos共标记增加中可以明显看出。我们提出,一个分子上不同的海马杏仁核回路是由生命早期的压力形成的,并调节情绪反应的动力学。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
High emotional reactivity is associated with activation of a molecularly distinct hippocampal-amygdala circuit modulated by the glucocorticoid receptor

Emotions are characterized not only by their valence but also by whether they are stable or labile. Yet, we do not understand the molecular or circuit mechanisms that control the dynamic nature of emotional responses. We have shown that glucocorticoid receptor overexpression in the forebrain (GRov) leads to a highly reactive mouse with increased anxiety behavior coupled with greater swings in emotional responses. This phenotype is established early in development and persists into adulthood. However, the neural circuitry mediating this lifelong emotional lability remains unknown. In the present study, optogenetic stimulation in ventral dentate gyrus (vDG) of GRov mice led to a greater range and a prolonged duration of anxiety behavior. cFos expression analysis showed that the amplified behavioral response to vDG activation in GRov mice is coupled to increased neuronal activity in specific brain regions. Relative to wild type mice, GRov mice displayed glutamatergic/GABAergic activation imbalance in ventral CA1 (vCA1) and selectively increased glutamatergic activation in the basal posterior amygdaloid complex. Moreover, forebrain GR overexpression led to increased activation of molecularly distinct subpopulations of neurons within the hippocampus and the posterior basolateral amygdala (pBLA) as evident from the increased cFos co-labeling in the calbindin1+ glutamatergic neurons in vCA1 and in the DARPP-32/Ppp1r1b+ glutamatergic neurons in pBLA. We propose that a molecularly distinct hippocampal-amygdala circuit is shaped by stress early in life and tunes the dynamics of emotional responses.

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来源期刊
Neurobiology of Stress
Neurobiology of Stress Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
9.40
自引率
4.00%
发文量
74
审稿时长
48 days
期刊介绍: Neurobiology of Stress is a multidisciplinary journal for the publication of original research and review articles on basic, translational and clinical research into stress and related disorders. It will focus on the impact of stress on the brain from cellular to behavioral functions and stress-related neuropsychiatric disorders (such as depression, trauma and anxiety). The translation of basic research findings into real-world applications will be a key aim of the journal. Basic, translational and clinical research on the following topics as they relate to stress will be covered: Molecular substrates and cell signaling, Genetics and epigenetics, Stress circuitry, Structural and physiological plasticity, Developmental Aspects, Laboratory models of stress, Neuroinflammation and pathology, Memory and Cognition, Motivational Processes, Fear and Anxiety, Stress-related neuropsychiatric disorders (including depression, PTSD, substance abuse), Neuropsychopharmacology.
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