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ErbB4 signaling in the prelimbic cortex regulates fear expression.

ErbB4 signaling in the prelimbic cortex regulates fear expression.

Authors :
Chen YH
Lan YJ
Zhang SR
Li WP
Luo ZY
Lin S
Zhuang JP
Li XW
Li SJ
Yang JM
Gao TM
Source :
Translational psychiatry [Transl Psychiatry] 2017 Jul 04; Vol. 7 (7), pp. e1168. Date of Electronic Publication: 2017 Jul 04.
Publication Year :
2017

Abstract

Many psychiatric diseases such as post-traumatic stress disorder (PTSD) are characterized by abnormal processing of emotional stimuli particularly fear. The medial prefrontal cortex (mPFC) is critically involved in fear expression. However, the molecular mechanisms underlying this process are largely unknown. Neuregulin-1 (NRG1) reportedly regulates pyramidal neuronal activity via ErbB4 receptors, which are abundant in parvalbumin (PV)-expressing interneurons in the PFC. In this study, we aimed to determine how NRG1/ErbB4 signaling in the mPFC modulates fear expression and found that tone-cued fear conditioning increased NRG1 expression in the mPFC. Tone-cued fear conditioning was inhibited following neutralization of endogenous NRG1 and specific inhibition or genetic ablation of ErbB4 in the prelimbic (PL) cortex but not in the infralimbic cortex. Furthermore, ErbB4 deletion specifically in PV neurons impaired tone-cued fear conditioning. Notably, overexpression of ErbB4 in the PL cortex is sufficient to reverse impaired fear conditioning in PV-Cre;ErbB4 <superscript>-/-</superscript> mice. Together, these findings identify a previously unknown signaling pathway in the PL cortex that regulates fear expression. As both NRG1 and ErbB4 are risk genes for schizophrenia, our study may shed new light on the pathophysiology of this disorder and help to improve treatments for psychiatric disorders such as PTSD.

Details

Language :
English
ISSN :
2158-3188
Volume :
7
Issue :
7
Database :
MEDLINE
Journal :
Translational psychiatry
Publication Type :
Academic Journal
Accession number :
28675393
Full Text :
https://doi.org/10.1038/tp.2017.139