4.3 Article

Effect of intra-BLA overexpression of IGF-1 on the expression of a contextual fear memory trace

期刊

HIPPOCAMPUS
卷 32, 期 10, 页码 765-775

出版社

WILEY
DOI: 10.1002/hipo.23465

关键词

basolateral amygdala; dendritic spines; dorsal hippocampus; fear memory; IGF-1 gene therapy

资金

  1. CONICET (Consejo Nacional de Investigaciones Cientificas y Tecnicas)
  2. FONCYT (Fondo para la Investigaci~on Cientifica y Tecnologia-Agencia Nacional de Promocion Cientifica y Tecnologica, Argentina)
  3. SECyT-UNC (Secretaria de Ciencia y Tecnologia-Universidad Nacional de Cordoba)

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Insulin-like growth factor 1 (IGF-1) plays a crucial role in learning and memory processes. Overexpressing IGF-1 in the basolateral amygdala (BLA) promotes the formation and expression of specific contextual fear memories. This overexpression also activates the ERK/MAPK pathway in the BLA and leads to structural plasticity changes in the dorsal hippocampus (DH).
Growth factors, such as insulin-like growth factor 1 (IGF-1), among others are known for their critical involvement in learning and memory processes. IGF-1 regulates cognitive functions, synapse density, neurotransmission, and adult neurogenesis and induces structural and synaptic plasticity-specific changes. Although IGF-1 has been suggested to participate in different memory processes, its role in memories associated with negative emotional experiences still remains to be elucidated. The principal aim of the present study was to test whether IGF-1 overexpression using adenoviral vectors in basolateral amygdala (BLA) influences both the expression and formation of contextual fear memory, as well as the hippocampal structural plasticity associated with such memory trace. We found that IGF-1 overexpression promotes the formation and expression of a specific contextual fear memory trace, and such effect persisted at least 7 days after recall. Moreover, the overexpression of this growth factor in BLA upregulates the activation of the ERK/MAPK pathway in this brain structure. In addition, intra-BLA IGF-1 overexpression causes dorsal hippocampus (DH) structural plasticity modifications promoting changes in the proportion of mature dendritic spines in the CA1 region, after a weak conditioning protocol. The present findings contribute to the knowledge underlying BLA-DH trace memory of fear and reveal important new insights into the neurobiology and neurochemistry of fear acquisition modulated by IGF-1 overexpression. The understanding of how IGF-1 modulates the formation of a fear contextual trace may pave the way for the development of novel therapeutic strategies focused on fear, anxiety, and trauma-related disorders.

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