title: A Selective Role for Lmo4 in Cue-Reward Learning.
abstract: The ability to use environmental cues to predict rewarding events is essential to survival. The basolateral amygdala (BLA) plays a central role in such forms of associative learning. Aberrant cue-reward learning is thought to underlie many psychopathologies, including addiction, so understanding the underlying molecular mechanisms can inform strategies for intervention. The transcriptional regulator LIM-only 4 (LMO4) is highly expressed in pyramidal neurons of the BLA, where it plays an important role in fear learning. Because the BLA also contributes to cue-reward learning, we investigated the role of BLA LMO4 in this process using Lmo4-deficient mice and RNA interference. Lmo4-deficient mice showed a selective deficit in conditioned reinforcement. Knockdown of LMO4 in the BLA, but not in the nucleus accumbens, recapitulated this deficit in wild-type mice. Molecular and electrophysiological studies identified a deficit in dopamine D2 receptor signaling in the BLA of Lmo4-deficient mice. These results reveal a novel, LMO4-dependent transcriptional program within the BLA that is essential to cue-reward learning.
authors.affiliation: Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas at Austin, Austin, Texas 78712, and Ernest Gallo Clinic and Research Center, Emeryville, California 94608 Rajani.Maiya@austin.utexas.edu.
authors.forename: Rajani
authors.identifier: http://orcid.org/0000-0003-1837-7175
authors.initials: R
authors.lastname: Maiya
authors.affiliation: Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas at Austin, Austin, Texas 78712, and.
authors.forename: Regina A
authors.initials: RA
authors.lastname: Mangieri
authors.affiliation: Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas at Austin, Austin, Texas 78712, and.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Morrisett
authors.affiliation: Ernest Gallo Clinic and Research Center, Emeryville, California 94608.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Heberlein
authors.affiliation: Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas at Austin, Austin, Texas 78712, and Ernest Gallo Clinic and Research Center, Emeryville, California 94608.
authors.forename: Robert O
authors.identifier: http://orcid.org/0000-0002-5345-4431
authors.initials: RO
authors.lastname: Messing
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001245:Association Learning / Q000502:physiology*; D066272:Basolateral Nuclear Complex / Q000166:cytology; D002755:Choice Behavior / Q000502:physiology*; D003216:Conditioning, Operant / Q000502:physiology; D003463:Cues; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology; D018408:Patch-Clamp Techniques; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism; D012201:Reward; D013395:Sucrose / Q000008:administration & dosage
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D060588:LIM Domain Proteins; C491976:Lmo4 protein, mouse; D034741:RNA, Small Interfering; D017448:Receptors, Dopamine D2; D049452:Green Fluorescent Proteins; D013395:Sucrose; D051057:Proto-Oncogene Proteins c-akt
keywords: basolateral amygdala; conditioned reinforcement; motivation; reward; transcription