SIM1 and Anxiety: This system has already been used to demonstrate the critical role for GABAergic signaling in the pathogenesis of RTT (Chao et al., 2010), as well as revealing non-overlapping roles for parvalbumin (PV)- and somatostatin (SOM)-expressing GABAergic neurons in behavior (Ito-Ishida et al., 2015), a role in feeding and aggression for Sim1-positive hypothalamic neurons (Fyffe et al., 2008), and a critical role for proper glutamatergic function in anxiety, tremor, and acoustic startle response (see companion paper Meng et al., 2016).