A Selective Role for Lmo4 in Cue–Reward Learning

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.