Lmo4 in the Basolateral Complex of the Amygdala Modulates Fear Learning

PLoS One

Amy W. Lasek¹  Rajani Maiya¹  Viktor Kharazia¹  Ulrike Heberlein¹ 

[1] Ernest Gallo Clinic and Research Center, Emeryville, California, United States of America

关键词: Mice;    Neurons;    Learning;    Animal behavior;    Hippocampus;    Fear conditioning;    Immunostaining;    Transcriptional control;   

DOI  :  10.1371/journal.pone.0034559

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

Pavlovian fear conditioning is an associative learning paradigm in which mice learn to associate a neutral conditioned stimulus with an aversive unconditioned stimulus. In this study, we demonstrate a novel role for the transcriptional regulator Lmo4 in fear learning. LMO4 is predominantly expressed in pyramidal projection neurons of the basolateral complex of the amygdala (BLC). Mice heterozygous for a genetrap insertion in the Lmo4 locus (Lmo4gt/+), which express 50% less Lmo4 than their wild type (WT) counterparts display enhanced freezing to both the context and the cue in which they received the aversive stimulus. Small-hairpin RNA-mediated knockdown of Lmo4 in the BLC, but not the dentate gyrus region of the hippocampus recapitulated this enhanced conditioning phenotype, suggesting an adult- and brain region-specific role for Lmo4 in fear learning. Immunohistochemical analyses revealed an increase in the number of c-Fos positive puncta in the BLC of Lmo4gt/+ mice in comparison to their WT counterparts after fear conditioning. Lastly, we measured anxiety-like behavior in Lmo4gt/+ mice and in mice with BLC-specific downregulation of Lmo4 using the elevated plus maze, open field, and light/dark box tests. Global or BLC-specific knockdown of Lmo4 did not significantly affect anxiety-like behavior. These results suggest a selective role for LMO4 in the BLC in modulating learned but not unlearned fear.

【 授权许可】

CC BY