Although we can only surmise that the reason for the increase in SOM-expressing interneuron activity is a potential compensatory mechanism to offset the glutamatergic dysregulation observed in HD mice (Cepeda et al., 2007; Bunner and Rebec, 2016), an unintended consequence of SOM upregulation is also an increase in spontaneous, activity-dependent, GABA synaptic activity (Cepeda et al., 2004). This evidence concerns the gene GRHL3 and Huntington disease.