Neuropeptide Y neurons in the nucleus accumbens modulate anxiety-like behavior

Neuropeptide Y neurons in the nucleus accumbens modulate anxiety-like behavior
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DOI:
10.1016/j.expneurol.2020.113216
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发表时间:
2020-01
影响因子:
5.3
通讯作者:
Shunji Yamada;M. S. Islam;N. V. Kooten;Sonny Bovee;Yoon-Mi Oh;A. Tsujimura;Yoshihisa Watanabe;Masaki Tanaka
Shunji Yamada;M. S. Islam;N. V. Kooten;Sonny Bovee;Yoon-Mi Oh;A. Tsujimura;Yoshihisa Watanabe;Masaki Tanaka
中科院分区:
医学2区
文献类型:
--
作者:
Shunji Yamada;M. S. Islam;N. V. Kooten;Sonny Bovee;Yoon-Mi Oh;A. Tsujimura;Yoshihisa Watanabe;Masaki Tanaka

文献摘要

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神经肽Y (NPY)是一种由36个氨基酸组成的神经肽,广泛表达于中枢神经系统,包括大脑皮层、伏隔核(NAc)和下丘脑。我们之前分析了仅表达5- ht2c受体未编辑RNA亚型的转基因小鼠的行为。这些小鼠NAc中NPY基因表达减少,表现出行为绝望,提示NAc中NPY神经元可能参与心境障碍;然而,它们在这种行为中的作用仍然未知。因此,在本研究中,我们使用NPY- cre小鼠和cre依赖性腺相关病毒,通过检测NAc NPY神经元特异性消融或激活的影响,研究NAc NPY神经元在焦虑样行为中的功能作用。与毒素治疗前相比,白喉毒素介导的NAc NPY神经元消融显著增加了开阔场地和升高的迷宫测试中的焦虑样行为。此外,与对照组小鼠相比,NAc NPY神经元的化学发生激活在两种行为测试中都减少了焦虑样行为。这些结果表明,NAc中的NPY神经元参与了小鼠焦虑的调节。
Neuropeptide Y (NPY) is a 36-amino acid neuropeptide that is widely expressed in the central nervous system, including the cerebral cortex, nucleus accumbens (NAc) and hypothalamus. We previously analyzed the behavior of transgenic mice exclusively expressing an unedited RNA isoform of the 5-HT2Creceptor. These mice showed decreased NPY gene expression in the NAc and exhibited behavioral despair, suggesting that NAc NPY neurons may be involved in mood disorder; however, their role in this behavior remained unknown. Therefore, in the present study, we investigated the functional role of NAc NPY neurons in anxiety-like behavior by examining the impact of specific ablation or activation of NAc NPY neurons using NPY-Cre mice and Cre-dependent adeno-associated virus. Diphtheria toxin-mediated ablation of NAc NPY neurons significantly increased anxiety-like behavior in the open field and elevated plus maze tests, compared with before toxin treatment. Moreover, chemogenetic activation of NAc NPY neurons reduced anxiety-like behavior in both behavioral tests compared with control mice. These results suggest that NPY neurons in the NAc are involved in the modulation of anxiety in mice.