While much of the past focus has been on ethanol effects on molecules and synapses, there has been increasing realization that these targets must be considered in the context of micro- and larger circuits. This concept has arisen from the findings that ethanol effects on cellular targets vary across brain regions due to differences in the molecular complement of different neurons and differences in ethanol sensitivity. For example, ethanol potentiates GIRK channel function in cerebellar granule neurons, but striatal MSNs do not express GIRK channels (Kobayashi et al., 1995), and thus, this mechanism would not be viable in these neurons. The variability in ethanol potentiation of delta-subunit-containing GABAA subunits (e.g., thalamus and hippocampus) also reinforces this point. In addition, there is increasing recognition of how different brain circuits contribute to behavior, and thus, we must understand ethanol’s effects on circuitry to fully appreciate the factors underlying the range of behavioral effects of the drug. The increasing appreciation of the larger circuitry in which individual brain regions participate has stimulated systems-level neuroscience in general and spurred increasing work at this level in the alcohol research field.
