Unlike in the hourglass

arena, in circular arenas there is no requirement for flies to make large-angled turns to follow the wall because the arena walls are concave. In circular arenas, the effect of the curved walls on the turn angle is clearly evident in the shift of the peak of the turn angle from 0° to 12° in the turn angle distribution in the boundary zone. Hence, small turn angle movement is not driving the wall-following behavior rather it is wall-following behavior that shapes Inhibitors,research,lifescience,medical the turn angles made by flies. Exploration of boundary Our data strongly suggest that the boundary of a circular arena is a primary object of exploration, as demonstrated by the ability of high-contrast walls to rescue the w1118 3-MA nmr attenuation of exploration deficit. It remains possible however

that the w1118 initial activity attenuation phenotype is not primarily due to poor visual acuity. Mutations in white are pleiotropic, resulting in defects in vision and also reduced levels of dopamine, Inhibitors,research,lifescience,medical serotonin, and histamine found with the Drosophila head (Borycz et al. 2008; Sitaraman et al. 2008). These biogenic amine reductions, in theory, may cause hyperactivity or learning deficits independent of visual exploration that could contribute to the w1118 activity attenuation phenotype (Sitaraman et al. 2008). The lower Inhibitors,research,lifescience,medical levels of dopamine found in the heads of the w1118 mutants is an unlikely source for the activity attenuation phenotype since reducing dopamine leads to lower levels of spontaneous activity (Liu et al. 2007; Riemensperger et al. 2011). Nevertheless, we believe that the most straightforward explanation for these data is that similar to blind norpA7, glass2, and the white-eyed Inhibitors,research,lifescience,medical brown1, scarlet1 double mutant (Liu et al. 2007), the activity attenuation defect in w1118

is due to the poor visual acuity associated with this mutation. Although Inhibitors,research,lifescience,medical this is likely due to the absence of screening pigments in the eyes of the w1118 mutants, the visual defect may also result from the reduced histamine found within this genotype since this neurotransmitter is used by photoreceptor neurons (Hardie 1987). In either or both cases, the opaque boundary likely rescues this activity attenuation phenotype due L-NAME HCl to the increased contrast it provides, allowing the w1118 mutants to detect the boundary and abrogate the novelty. In the concentric inner circle and the internal corner arenas, the flies were preferentially attending to the arena boundary and not just vertical walls. This suggests that there is a specific feature of the boundary that the flies attend. When the flies are actively exploring the arena boundary, they bypass shelter, suggesting this is not a primary goal for the exploration. Moreover, our turn angle calculations and hourglass experiments indicate that wall-following behavior shapes turn angles in the boundary zone and not vice versa.