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Neurobiol Learn Mem. 2018 Apr;150:93-98. doi: 10.1016/j.nlm.2018.03.007. Epub 2018 Mar 10.

Development of the fear regulation system from early adolescence to young adulthood in female mice.

Author information

1
Department of Pharmacotherapeutics, Showa Pharmaceutical University, 3-3165, Higashi-tamagawagakuen, Machida, Tokyo 194-8543, Japan; Department of Cognitive Behavioral Physiology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba, Chiba 260-8670, Japan; Department of Ultrastructural Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan. Electronic address: smatsuda@ac.shoyaku.ac.jp.
2
Department of Cognitive Behavioral Physiology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba, Chiba 260-8670, Japan; Research Center for Child Mental Development, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba, Chiba 260-8670, Japan.
3
Department of Cognitive Behavioral Physiology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba, Chiba 260-8670, Japan; Center for Medical Sciences, Ibaraki Prefectural University of Health Sciences, 4669-2 Ami, Ami-machi, Inashiki-gun, Ibaraki 300-0394, Japan.
4
Department of Cognitive Behavioral Physiology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba, Chiba 260-8670, Japan.

Abstract

Onset of fear-related disorders such as post-traumatic stress disorder is enhanced from adolescence until adulthood. However, the biological mechanisms underlying this vulnerability remain unclear. Therefore, we investigated contextual fear memory and extinction in 4-, 6-, 8-, 10-, and 15-week-old female mice. We also measured phosphorylation of ERK2 in the medial prefrontal cortex (mPFC) and the dorsal hippocampus following fear conditioning or extinction in 6- and 15-week-old mice. We found that 10- and 15-week-old mice showed stronger fear memory and more resistance to fear extinction than 6-week-old mice. Moreover, 15-week-old mice showed lower ERK2 phosphorylation levels following fear extinction in the mPFC than those 6 weeks old. Our results suggest that female mice acquire strong fear memory and resistance to fear extinction throughout adulthood, which may be related to alteration in ERK2 activation in the mPFC.

KEYWORDS:

Age differences; Extracellular signal-regulated kinase (ERK); Fear extinction; Fear memory; Females

PMID:
29535045
DOI:
10.1016/j.nlm.2018.03.007

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