下丘脑背内侧核对焦虑的调控机制研究
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摘要
下丘脑背内侧核(Dorsomedial Hypothalamic Nucleus,DMH)是自主神经系统的重要组成部分,同时与调控焦虑情绪的边缘系统存在广泛联系。然而,DMH调控焦虑等负性情绪的细胞机制目前尚不明确。该文应用光遗传技术特异性调控小鼠的谷氨酸能神经元和γ-氨基丁酸能神经元发现,兴奋DMH的谷氨酸能和γ-氨基丁酸能神经元均能显著诱发焦虑样行为和心率上升,抑制两种神经元均能抑制焦虑样行为并降低心率。该研究证实了DMH特定类型的神经细胞对焦虑的双向调控作用,并有望为神经精神疾病的临床干预提供新的调控靶点。
Dorsomedial hypothalamic nucleus(DMH) is an important component of autonomic nervous system, which has extensive connections with limbic system. DMH may participates in the regulation of negative emotions, such as anxiety and fear. However, the cellular mechanisms are still unknown. In this study, elevated plus maze and open filed tests were performed, and a bidirectional effect of optogenetic modulation on behaviors was found. Activating the DMH glutamatergic or gamma-aminobutyric acid(GABAergic) neurons leading to the anxiety-like behavior and increasing of heart rate, while optical inhibition significantly suppressed the anxiety-like behavior and decreased heart rate. These findings may provide new targets for clinical therapy for neuropsychiatric disorders.
Dorsomedial hypothalamic nucleus(DMH) is an important component of autonomic nervous system, which has extensive connections with limbic system. DMH may participates in the regulation of negative emotions, such as anxiety and fear. However, the cellular mechanisms are still unknown. In this study, elevated plus maze and open filed tests were performed, and a bidirectional effect of optogenetic modulation on behaviors was found. Activating the DMH glutamatergic or gamma-aminobutyric acid(GABAergic) neurons leading to the anxiety-like behavior and increasing of heart rate, while optical inhibition significantly suppressed the anxiety-like behavior and decreased heart rate. These findings may provide new targets for clinical therapy for neuropsychiatric disorders.
引文
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[13]Likhtik E,Stujenske JM,Topiwala MA,et al Prefrontal entrainment of amygdala activity signals safety in learned fear and innate anxiety[J].Nature Neuroscience,2013,17(1):106-113.
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[15]Gross CT,Canteras NS.The many paths to fear[J]Nature Review Neuroscience,2012,13(9):651-658.
[16]Santos JM,Macedo CE,Brand?o ML.Gabaergic mechanisms of hypothalamic nuclei in the expression of conditioned fear[J].Neurobiology of Learning and Memory,2008,90(3):560-568.
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[19]Wong LC,Wang L,D’Amour JA,et al.Effective modulation of male aggression through lateral septum to medial hypothalamus projection[J].Current Biology,2016,26(5):593-604.
[20]Abreu AR,Molosh AI,Johnson PL,et al.Role of medial hypothalamic orexin system in panic,phobia and hypertension[J].Brain Research,2018,doi:10.1016/j.brainres.2018.09.010.
[21]Zoeram SB,Salmani ME,Lashkarbolouki T,et al.Hippocampal orexin receptor blocking prevented the stress induced social learning and memory deficits[J].Neurobiology of Learning and Memory2019,157:12-23.
[22]Root CM,Denny CA,Hen R,et al.The participation of cortical amygdala in innate,odour-driven behaviour[J].Nature,2014,515(7526):269-273.
[23]Li L,de La Serre CB,Zhang N,et al.Knockdown of neuropeptide Y in the dorsomedial hypothalamus promotes hepatic insulin sensitivity in male rats[J]Endocrinology,2016,157(12):4842-4852.
[24]Crick FH.Thinking about the brain[J].Scientific American,1979,241(3):219-232.
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[26]Nascimento JOG,Kikuchi LS,Bortoli VC,et al.Dorsomedial hypothalamus serotonin 1A receptors mediate a panic-related response in the elevated T-maze[J].Brain Research Bulletin,2014,109:39-45.
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