title: Lmo4 in the basolateral complex of the amygdala modulates fear learning.
abstract: 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.
authors.affiliation: Ernest Gallo Clinic and Research Center, Emeryville, California, United States of America. rmaiya@gallo.ucsf.edu
authors.forename: Rajani
authors.initials: R
authors.lastname: Maiya
authors.forename: Viktor
authors.initials: V
authors.lastname: Kharazia
authors.forename: Amy W
authors.initials: AW
authors.lastname: Lasek
authors.forename: Ulrike
authors.initials: U
authors.lastname: Heberlein
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000679:Amygdala / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D003213:Conditioning, Psychological / Q000502:physiology*; D003463:Cues; D005239:Fear / Q000502:physiology / Q000523:psychology*; D055785:Gene Knockdown Techniques; D060588:LIM Domain Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D021381:Protein Transport
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D060588:LIM Domain Proteins; C491976:Lmo4 protein, mouse