Convergent effects of mouse Pet-1 deletion and human PET-1 variation on amygdala fear and threat processing.
Exp Neurol
; 250: 260-9, 2013 Dec.
Article
en En
| MEDLINE
| ID: mdl-24100022
ABSTRACT
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.
Palabras clave
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
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
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Proteínas Nucleares
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Predisposición Genética a la Enfermedad
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Proteínas de Unión al ADN
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Emociones
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Miedo
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Amígdala del Cerebelo
Límite:
Adult
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Animals
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Female
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Humans
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Male
Idioma:
En
Revista:
Exp Neurol
Año:
2013
Tipo del documento:
Article