Chronic alcohol consumption changes gene expression, likely causing persistent
remodeling of synaptic structures via altered translation of mRNAs within synaptic
compartments of the cell. We profiled the transcriptome from synaptoneurosomes (SNs) and
paired total homogenates (THs) from mouse amygdala following chronic voluntary alcohol
consumption. In SN, both the number of alcohol-responsive mRNAs and the magnitude of
fold-change were greater than in THs, including many GABA-related mRNAs upregulated in
SNs. Furthermore, SN gene co-expression analysis revealed a highly connected network,
demonstrating coordinated patterns of gene expression and highlighting alcohol-responsive
biological pathways, such as long-term potentiation, long-term depression, glutamate
signaling, RNA processing and upregulation of alcohol-responsive genes within neuroimmune
modules. Alterations in these pathways have also been observed in the amygdala of human
alcoholics. SNs offer an ideal model for detecting intricate networks of coordinated
synaptic gene expression and may provide a unique system for investigating therapeutic
targets for the treatment of alcoholism.