期刊
EXPERIMENTAL NEUROLOGY
卷 250, 期 -, 页码 260-269出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.expneurol.2013.09.025
关键词
Basolateral amygdala; Medial prefrontal cortex; Fear conditioning; Serotonin; FEV
资金
- US-Israel Binational Science Foundation [2007096]
- Intramural Research Program of the National Institute on Alcoholism and Alcohol Abuse [Z01-AA000411]
- Duke University
Serotonin is critical for shaping the development of neural circuits regulating emotion. Pet-1 (FEV-1) is an ETS-domain transcription factor essential for differentiation and forebrain targeting of serotonin neurons. Constitutive P knockout (KO) causes major loss of serotonin neurons and forebrain serotonin availability, and behavioral abnormalities. We phenotyped Pet-1 KO mice for fear conditioning and extinction, and on a battery of assays for anxiety- and depression-related behaviors. Morphology of Golgi-stained neurons in basolateral amygdala (BLA) and prelimbic cortex was examined. Using human imaging genetics, a common variant (rs860573) in the PET-1 (FEY) gene was tested for effects on threat-related amygdala reactivity and psychopathology in 88 Asian-ancestry subjects. Pet-1 KO mice exhibited increased acquisition and expression of fear, and elevated fear recovery following extinction, relative to wild-type (WT). BLA dendrites of Pet-1 KO mice were significantly longer than in WT. Human PET-1 variation associated with differences in amygdala threat processing and psychopathology. This novel evidence for the role of Pet-1 in fear processing and dendritic organization of amygdala neurons and in human amygdala threat processing extends a growing literature demonstrating the influence of genetic variation in the serotonin system on emotional regulation via effects on structure and function of underlying corticolimbic circuitry. (C) 2013 Elsevier Inc. All rights reserved.
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