Elucidating the subcellular pathways that regulate G protein-gated inwardly rectifying potassium (GIRK or Kir3) channels is important for understanding control of neural circuits in the brain. Here, we show for the first time that SNX27 plays a key role in regulating neuronal excitability of DA neurons, likely through control of GIRK channel trafficking. Loss of SNX27 leads to reduced GABABR-activated GIRK currents, which was sufficient to alter the stimulatory response to cocaine. Altered VTA inhibitory control has been implicated in a number of psychiatric disorders, including response to addictive drugs (Lüscher and Malenka, 2011), aversive stimuli (Jhou et al., 2009), and depression (Tye et al., 2012). Targeting inhibitory signaling may emerge as an alternative strategy for novel therapeutic interventions for treating addiction (Lujan et al., 2013).
