As mean values in circadian activity analysis may conceal some VE-822 inquirer salient features, we undertook an individual visual inspection of the behavior of each fly and found that about half of DmIh mutant flies lack the bimodal pattern of activity , resembling the sustained activity shown by wild type flies during the subjective day in DD . To get a more objective measure of this behavior, we performed Fourier transformation analysis on control and mutant flies, which provides a quantitative assessment of the rhythmicity at the predominant frequency: normal behavior in LD gives a predominant frequency of 12 hours due to the bimodal rhythmic pattern, while a sustained activity during the light period is expected to yield a predominant frequency of 24 hours. Indeed, while 98.4% of control flies had a predominant frequency of 12 hours, in DmIh mutants flies the predominant frequency was 24 hours in 41.1% of the flies. This result suggests an association between the pattern of dopamine oscillation and the pattern of locomotor activity, both being affected by light. Taken together, our results strongly suggest that, in Drosophila, Ih current is necessary to prevent an overproduction of dopamine in dark conditions. In addition, we can infer from our results that light input influences cycling of dopamine in an Ih current dependent manner. DmIh is expressed in retinal receptors , but lack of this current does not prevent light entrainment of circadian rhythms, indicating that mutant flies are not severely impaired for light detection. Drosophila has proven to be a good model to study sleep , and dopamine has emerged as a key modulator of this physiological state. It has been shown that lengthening the dopamine effect in target neurons, as in flies with a mutation in the dopamine transporter encoding-gene fumin , leads to a severe reduction of sleep , even though the number of sleep episodes increases considerably . In addition, high dopamine levels in flies lacking the fragile X mental retardation protein increase the number of sleep episodes . Given the anomalous dopamine levels in DmIh mutants we expected to see a change in the rest-activity pattern of these flies. Activity was monitored in individual flies in a 12 h light:dark cycle and rest:activity parameters were analyzed . Sleep state was defined as bouts of uninterrupted five minutes of inactivity. The LY2157299 in vivo non-sleeping periods were considered as waking state. During the day, total length of the waking period is not different between control and mutant flies. However, a reduction in beamcrossing counts per active minute causes a decrease in the total activity of mutant flies , suggesting that DmIh deficient flies are hypoactive. Surprisingly, at nighttime mutant flies show a significant increase in the counts per active minute when compared with control flies, but total activity is not different .