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Exp Neurol. 2013 Dec;250:260-9. doi: 10.1016/j.expneurol.2013.09.025. Epub 2013 Oct 4.

Convergent effects of mouse Pet-1 deletion and human PET-1 variation on amygdala fear and threat processing.

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Department of Psychological and Brain Sciences, Center for the Integrative Study of Animal Behavior, Indiana University, Bloomington, IN, USA. Electronic address:

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  • Exp Neurol. 2014 Feb;252:104.


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 Pet-1 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 (FEV) 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.


5-HTT; BLA; Basolateral amygdala; EtOH; FEV; Fear conditioning; KO; Medial prefrontal cortex; PL; PTSD; Pet-1, FEV; Pheochromocytoma 12 ets; Serotonin; Tph2; basolateral amygdala; ethanol; knockout; posttraumatic stress disorder; prelimbic cortex; the serotonin transporter; tryptophan hydroxylase-2; ventromedial prefrontal cortex; vmPFC

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