cFOS as a biomarker of activity maturation in the hippocampal formation Articles uri icon

publication date

  • July 2023

start page

  • 1

end page

  • 18

volume

  • 17

International Standard Serial Number (ISSN)

  • 1662-4548

Electronic International Standard Serial Number (EISSN)

  • 1662-453X

abstract

  • 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.

subjects

  • Biology and Biomedicine

keywords

  • cfos; waking; hippocampus; entorhinal cortex; septum; anterior thalamic nuclei; head; direction system; theta rhythm