Here, we illustrate that alcohol causes a rapid increase in miR-9 expression in these neurons. Only BK mRNAs containing a miR-9 binding site in their 3’UTRs are degraded, while others are spared. This reorganization of neuronal BK splice variants leads to a change in BK channel isoform profile consistent with the development of tolerance. This mechanism was found to affect ten additional alcohol-relevant miR-9 targets in the brain, providing a potential mechanism for an integrated response to the drug. The data describe a remarkably fast and elegant mechanism of alcohol multiplex regulation of neuronal alcohol tolerance.
