A hippocampal insulin-growth factor 2 pathway regulates the extinction of fear memories
Identificadores
Identificadores
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Fecha de publicación
2011Título de revista
The EMBO Journal
Tipo de contenido
Artigo
DeCS
factor II de crecimiento insulinoide | hipocampo | miedo | regulación de la expresión génica | análisis de secuencias por matrices de oligonucleótidos | transducción de señales luminosas | proteína 1 de unión a factores de crecimiento insulinoide | extinción psicológica | memoria | neuronas | proliferación celular | factores de tiempo | modelos biológicosMeSH
Memory | Hippocampus | Insulin-Like Growth Factor Binding Protein 1 | Insulin-Like Growth Factor II | Neurons | Cell Proliferation | Extinction, Psychological | Fear | Models, Biological | Light Signal Transduction | Oligonucleotide Array Sequence Analysis | Time Factors | Gene Expression RegulationResumen
Extinction learning refers to the phenomenon that a previously learned response to an environmental stimulus, for example, the expression of an aversive behaviour upon exposure to a specific context, is reduced when the stimulus is repeatedly presented in the absence of a previously paired aversive event. Extinction of fear memories has been implicated with the treatment of anxiety disease but the molecular processes that underlie fear extinction are only beginning to emerge. Here, we show that fear extinction initiates upregulation of hippocampal insulin-growth factor 2 (Igf2) and downregulation of insulin-growth factor binding protein 7 (Igfbp7). In line with this observation, we demonstrate that IGF2 facilitates fear extinction, while IGFBP7 impairs fear extinction in an IGF2-dependent manner. Furthermore, we identify one cellular substrate of altered IGF2 signalling during fear extinction. To this end, we show that fear extinction-induced IGF2/IGFBP7 signalling promotes the survival of 17-19-day-old newborn hippocampal neurons. In conclusion, our data suggest that therapeutic strategies that enhance IGF2 signalling and adult neurogenesis might be suitable to treat disease linked to excessive fear memory.