Hes1 expression in mature neurons in the adult mouse brain is required for normal behaviors
Hes1 expression in mature neurons in the adult mouse brain is required for normal behaviors
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DOI：
10.1038/s41598-019-44698-y
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发表时间：
2019-06-03
影响因子：
4.6
通讯作者：
Kageyama, Ryoichiro
中科院分区：
文献类型：
--
作者：
Matsuzaki, Tadanobu;Yoshihara, Toru;Kageyama, Ryoichiro
Hes 1作为Notch信号通路的重要效应子调节神经干/祖细胞的维持和增殖。虽然Notch信号也参与了成熟神经元在学习和记忆中的功能，以及精神障碍如精神分裂症和双相情感障碍的危险因素，但Hes 1在成熟神经元中的体内作用仍然未知。在这里，我们发现，Hes 1表达的兴奋性和抑制性神经元在成年小鼠大脑的子集，Hes 1的表达是由神经元刺激诱导。此外，Hes 1在兴奋性神经元中的失活导致异常的恐惧和焦虑行为伴随着杏仁核中更高的神经元兴奋性，而Hes 1在抑制性神经元中的失活导致社交性和持续性倾向增加。这些结果表明，Hes 1不仅在成年大脑的兴奋性神经元中，而且在抑制性神经元中对正常行为具有重要的功能。
Hes1 regulates the maintenance and proliferation of neural stem/progenitor cells as an essential effector of the Notch signaling pathway. Although Notch signaling is also involved in the functions of mature neurons in learning and memory and in the risk factors for mental disorders such as schizophrenia and bipolar disorder, the in-vivo role of Hes1 in mature neurons remains unknown. Here, we found that Hes1 is expressed by subsets of both excitatory and inhibitory neurons in the adult mouse brain, and that Hes1 expression is induced by neuronal stimulation. Furthermore, inactivation of Hes1 in excitatory neurons resulted in abnormal fear and anxiety behaviors concomitantly with higher neuronal excitability in the amygdala, while inactivation of Hes1 in inhibitory neurons resulted in increased sociability and perseverative tendencies. These results indicated that Hes1 is functionally important for normal behaviors not only in excitatory neurons but also in inhibitory neurons in the adult brain.