Our discussion has largely focused on those changes in gene expression that are similar across the three brain regions. Our argument for taking this perspective is that these changes are the “broad” targets for manipulation. Included in these broad targets are core genes, including hub nodes, associated with glutamate receptor signaling and synaptic plasticity. We have also confirmed (see Colville et al., 2017) that selection for ethanol preference in HS-CC mice involves a large cohort of clustered protocadherins. This differs from selection for binge ethanol consumption where we have observed that selection for “drinking in the dark” involves numerous extra-cellular matrix genes such as collagens and matrix metalloproteases (Iancu et al., 2018). “Narrow” sense targets for manipulations will include those selection based changes that are regionally unique. For example, we observed that in the CeA, the expression of Nrtk2 which encodes TrkB, a receptor for Bdnf, moves from non-hub status in the Low selected line to hub status in the High line. Numerous studies have linked the regulation of ethanol consumption to the regulation of Bdnf function; Darcq et al.
