Horii-Hayashi Noriko, Masuda Kazuya, Kato Taika, Kobayashi Kenta, Inutsuka Ayumu, Nambu Miyu F, Tanaka Kazumasa Z, Inoue Koichi, Nishi Mayumi
Anatomy and Cell Biology, Department of Medicine, Nara Medical University, Kashihara, Japan.
Section of Viral Vector Development, National Institute for Physiological Sciences, Okazaki, Japan.
Front Behav Neurosci. 2024 Jan 5;17:1289520. doi: 10.3389/fnbeh.2023.1289520. eCollection 2023.
The security of animal habitats, such as burrows and nests, is vital for their survival and essential activities, including eating, mating, and raising offspring. Animals instinctively exhibit defensive behaviors to protect themselves from imminent and potential threats. In 1963, researchers reported wild rats sealing the entrances to their burrows from the inside using materials such as mud, sand, and vegetation. This behavior, known as "entrance sealing (ES)," involves repetitive movements of their nose/mouth and forepaws and is likely a proactive measure against potential intruders, which enhances burrow security. These observations provide important insights into the animals' ability to anticipate potential threats that have not yet occurred and take proactive actions. However, this behavior lacks comprehensive investigation, and the neural mechanisms underpinning it remain unclear. Hypothalamic perifornical neurons expressing urocortin-3 respond to novel objects/potential threats and modulate defensive responses to the objects in mice, including risk assessment and burying. In this study, we further revealed that chemogenetic activation of these neurons elicited ES-like behavior in the home-cage. Furthermore, behavioral changes caused by activating these neurons, including manifestations of ES-like behavior, marble-burying, and risk assessment/burying of a novel object, were effectively suppressed by selective serotonin-reuptake inhibitors. The c-Fos analysis indicated that ES-like behavior was potentially mediated through GABAergic neurons in the lateral septum. These findings underscore the involvement of hypothalamic neurons in the anticipation of potential threats and proactive defense against them. The links of this security system with the manifestation of repetitive/stereotypic behaviors and the serotonergic system provide valuable insights into the mechanisms underlying the symptoms of obsessive-compulsive disorder.
动物栖息地的安全，如洞穴和巢穴，对它们的生存以及进食、交配和养育后代等基本活动至关重要。动物会本能地表现出防御行为以保护自己免受迫在眉睫的和潜在的威胁。1963年，研究人员报告称野生大鼠会用泥土、沙子和植被等材料从内部封闭洞穴入口。这种行为被称为“入口封闭（ES）”，涉及鼻子/嘴巴和前爪的重复动作，很可能是针对潜在入侵者的一种主动措施，可增强洞穴的安全性。这些观察结果为动物预测尚未发生的潜在威胁并采取主动行动的能力提供了重要见解。然而，这种行为缺乏全面的研究，其背后的神经机制仍不清楚。表达urocortin - 3的下丘脑室周神经元对新物体/潜在威胁做出反应，并调节小鼠对这些物体的防御反应，包括风险评估和掩埋。在本研究中，我们进一步发现这些神经元的化学遗传激活在家笼中引发了类似ES的行为。此外，激活这些神经元引起的行为变化，包括类似ES行为、大理石掩埋以及对新物体的风险评估/掩埋的表现，被选择性5 - 羟色胺再摄取抑制剂有效抑制。c - Fos分析表明，类似ES的行为可能是通过外侧隔中的γ-氨基丁酸能神经元介导的。这些发现强调了下丘脑神经元在预测潜在威胁和对其进行主动防御中的作用。这个安全系统与重复/刻板行为表现以及血清素能系统的联系为强迫症症状的潜在机制提供了有价值的见解。
