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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.

Lmo4 in the Basolateral Complex of the Amygdala Modulates Fear Learning