内侧隔区γ-氨基丁酸能投射神经元促进物体探索行为和2型θ节律。
Medial septal GABAergic projection neurons promote object exploration behavior and type 2 theta rhythm.
作者信息
Gangadharan Gireesh, Shin Jonghan, Kim Seong-Wook, Kim Angela, Paydar Afshin, Kim Duk-Soo, Miyazaki Taisuke, Watanabe Masahiko, Yanagawa Yuchio, Kim Jinhyun, Kim Yeon-Soo, Kim Daesoo, Shin Hee-Sup
机构信息
Center for Cognition and Sociality, Institute for Basic Science, Daejeon 305-308, Korea;
Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles David Geffen School of Medicine, Los Angeles, CA 90095-6948;
出版信息
Proc Natl Acad Sci U S A. 2016 Jun 7;113(23):6550-5. doi: 10.1073/pnas.1605019113. Epub 2016 May 20.
Exploratory drive is one of the most fundamental emotions, of all organisms, that are evoked by novelty stimulation. Exploratory behavior plays a fundamental role in motivation, learning, and well-being of organisms. Diverse exploratory behaviors have been described, although their heterogeneity is not certain because of the lack of solid experimental evidence for their distinction. Here we present results demonstrating that different neural mechanisms underlie different exploratory behaviors. Localized Cav3.1 knockdown in the medial septum (MS) selectively enhanced object exploration, whereas the null mutant (KO) mice showed enhanced-object exploration as well as open-field exploration. In MS knockdown mice, only type 2 hippocampal theta rhythm was enhanced, whereas both type 1 and type 2 theta rhythm were enhanced in KO mice. This selective effect was accompanied by markedly increased excitability of septo-hippocampal GABAergic projection neurons in the MS lacking T-type Ca(2+) channels. Furthermore, optogenetic activation of the septo-hippocampal GABAergic pathway in WT mice also selectively enhanced object exploration behavior and type 2 theta rhythm, whereas inhibition of the same pathway decreased the behavior and the rhythm. These findings define object exploration distinguished from open-field exploration and reveal a critical role of T-type Ca(2+) channels in the medial septal GABAergic projection neurons in this behavior.
探究驱力是所有生物体中最基本的情绪之一,由新奇刺激引发。探究行为在生物体的动机、学习和幸福感中起着基础性作用。尽管由于缺乏区分不同探究行为的可靠实验证据,其异质性尚不确定,但已有多种探究行为被描述。在此,我们展示的结果表明,不同的神经机制是不同探究行为的基础。内侧隔区(MS)局部敲低Cav3.1可选择性增强物体探究,而基因敲除(KO)小鼠则表现出增强的物体探究以及旷场探究。在MS敲低小鼠中,仅2型海马θ节律增强,而在KO小鼠中,1型和2型θ节律均增强。这种选择性效应伴随着缺乏T型钙通道的MS中隔海马GABA能投射神经元兴奋性的显著增加。此外,野生型小鼠中隔海马GABA能通路的光遗传学激活也选择性增强了物体探究行为和2型θ节律,而抑制同一通路则降低了该行为和节律。这些发现定义了与旷场探究不同的物体探究,并揭示了T型钙通道在内侧隔区GABA能投射神经元在该行为中的关键作用。
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