cFOS as a biomarker of activity maturation in the hippocampal formation.
cFOS as a biomarker of activity maturation in the hippocampal formation.
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DOI：
10.3389/fnins.2023.929461
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发表时间：
2023
影响因子：
4.3
通讯作者：
Colonnese, Matthew T.
中科院分区：
文献类型：
--
作者：
Pompeiano, Maria;Colonnese, Matthew T.
关键词：
我们探索了 cFOS 表达作为海马和内嗅皮层扩展网络中“静息态”清醒活动功能发育标志物的潜力。我们在产后第 5、9、13 和 17 天以及成年期检查了睡眠和清醒的小鼠。我们发现即使在 5 天大时，cFOS 的表达也是状态依赖性的，只有在清醒的小鼠中才发生可靠的染色。即使在清醒时，cFOS 表达在 P5 时也很少且很弱。间隔核、内嗅皮层 (L)2 和前背丘脑的特殊之处在于，它们在 P5 时具有与成年期相似或更高的强 cFOS 表达。在齿状回、内嗅皮层 L6、后下托 L4-6、腹侧下托、乳头上核和下丘脑后核中也观察到显着的 P5 表达。这些区域的表达随着年龄的增长而增强，并且新区域的表达在 P9 和 P13 时逐渐增加，此时许多区域的整体表达模式在质量上与成人相似。六个区域——CA1、背下托、后下托、L2-3、reuniens 核以及鼻周和鼻后皮质——发育非常晚，大多数在 P17 后才达到成人水平。我们的研究结果支持许多发展原则。首先，睡眠期间肌肉抽搐引起的早期自发活动模式不会在扩展的海马网络中诱导强大的 cFOS 表达。其次，cFOS 表达的发展遵循三突触回路的渐进激活，而不是出生日期或细胞成熟。第三，我们揭示了以自我为中心的头部方向和 theta 节律回路的组成部分，它们是前脑中最早的 cFOS 活跃回路。我们的结果表明，cFOS 染色可以为海马形成活动的发展提供可靠且敏感的生物标志物，特别是在获得正常清醒状态和同步节律（如 θ 和 γ）方面。
We explored the potential for cFOS expression as a marker of functional development of “resting-state” waking activity in the extended network of the hippocampus and entorhinal cortex. We examined sleeping and awake mice at (P)ostnatal days 5, 9, 13, and 17 as well as in adulthood. We find that cFOS expression is state-dependent even at 5 days old, with reliable staining occurring only in the awake mice. Even during waking, cFOS expression was rare and weak at P5. The septal nuclei, entorhinal cortex layer (L)2, and anterodorsal thalamus were exceptional in that they had robust cFOS expression at P5 that was similar to or greater than in adulthood. Significant P5 expression was also observed in the dentate gyrus, entorhinal cortex L6, postsubiculum L4-6, ventral subiculum, supramammillary nucleus, and posterior hypothalamic nucleus. The expression in these regions grew stronger with age, and the expression in new regions was added progressively at P9 and P13 by which point the overall expression pattern in many regions was qualitatively similar to the adult. Six regions—CA1, dorsal subiculum, postsubiculum L2-3, reuniens nucleus, and perirhinal and postrhinal cortices—were very late developing, mostly achieving adult levels only after P17. Our findings support a number of developmental principles. First, early spontaneous activity patterns induced by muscle twitches during sleep do not induce robust cFOS expression in the extended hippocampal network. Second, the development of cFOS expression follows the progressive activation along the trisynaptic circuit, rather than birth date or cellular maturation. Third, we reveal components of the egocentric head-direction and theta-rhythm circuits as the earliest cFOS active circuits in the forebrain. Our results suggest that cFOS staining may provide a reliable and sensitive biomarker for hippocampal formation activity development, particularly in regard to the attainment of a normal waking state and synchronizing rhythms such as theta and gamma.
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