A second Gal4 line, E605-Gal4, contains PERin and displays the same behavioral phenotypes upon neural inactivation or activation ( Figure S4). These data suggest that there is a reciprocal buy VE-821 balance between feeding initiation and locomotion mediated by PERin activity. To test whether the act of proboscis extension sufficed to inhibit locomotion, we immobilized the proboscis in an extended or retracted position with wax. Wild-type flies with

extended proboscises moved significantly less (Figure 7D), arguing that motor activity or proprioceptive feedback from the proboscis inhibits locomotion. Consistent with this, immobilizing the proboscis in a retracted state partially rescued the locomotor defect of flies with inactivated PERin MK-2206 clinical trial neurons (Figure 7D). Thus, proboscis extension feeds back onto circuits to inhibit locomotion, allowing for mutually exclusive behaviors. Many behaviors are mutually exclusive, with the decision to commit to one behavior excluding the selection of others. Here, we show that feeding initiation and locomotion are mutually

exclusive behaviors and that activity in a single pair of interneurons influences this behavioral choice. PERin neurons are activated by stimulation of mechanosensory neurons and activation of PERin inhibits proboscis extension, suggesting that they inhibit feeding while the animal is walking. Consistent with this, leg removal or immobilization enhances proboscis extension probability and this is inhibited by increased PERin activity. The opposite behavior is elicited upon inhibiting activity in PERin neurons: animals show constitutive proboscis extension at the expense of locomotion. This work shows that activity in a single pair of interneurons dramatically influences the choice between feeding initiation and movement. The precise mechanism MRIP of activation of PERin neurons remains to be determined. PERin dendrites reside in the first leg neuromere, suggesting that they process information from the legs. Stimulation of leg chemosensory bristles with sucrose or quinine or activation of sugar, bitter, or water neurons using

optogenetic approaches did not activate PERin neurons, nor did satiety state change tonic activity. Stimulation of sensory nerves into the ventral nerve cord and stimulation of mechanosensory neurons, using a nompC driver, activated PERin. In addition, by monitoring activity of PERin while flies moved their legs, we demonstrated that activity was coincident with movement. These studies argue that PERin is activated by nongustatory cues in response to movement, likely upon detection of mechanosensory cues. Additional cues may also activate PERin. Studies of behavioral exclusivity in other invertebrate species suggest two mechanisms by which one behavior suppresses others (Kristan and Gillette, 2007). One strategy is by competition between command neurons that activate dedicated circuits for different behaviors.