TRANSCRIPTION COFACTOR LIM-ONLY 4 (LMO4) AND ALCOHOL CONSUMPTION AND REWARD

Our work implicates a complex and brain region-specific role for the transcription co-factor Lim-Only 4 in regulating alcohol consumption and reward. shRNA mediated knockdown of LMO4 in the BLA reduces alcohol consumption and reward whereas knockdown in the NAc leads to a modest enhancement in alcohol intake in mice. Whole genome sequencing of the BLA and NAc from WT and Lmo4-deficient mice revealed several transcriptional targets of LMO4 with very little overlap between the NAc and the BLA which may underlie the contrasting alcohol consumption phenotypes observed. Transcriptional targets of LMO4 include the kappa opioid receptor (KOR) and genes related to the extracellular matrix. Future studies will further explore further the relationship between LMO4 and its transcriptional targets in regulating alcohol intake and also determine how the LMO4-regulated transcriptome alters with alcohol intake.

Investigating the molecular mechanisms that underlie social defeat stress-induced escalation of alcohol consumption. This project will use cutting-edge molecular genetic tools including whole genome sequencing and targeted recombination in activated populations (TRAP) to investigate molecular, cellular, and circuit mechanisms that underlie social stress-induced escalation of alcohol consumption. We will also explore the role of the Kappa/Dynorphin system in mediating stress-induced escalation of alcohol intake.