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. 2018 Dec 6;19(12):3911. doi: 10.3390/ijms19123911

Figure 1.

Figure 1

Locomotor activity and organization of the circadian clock and dopaminergic system in the brain of D. melanogaster (A,B) Locomotor activity (mean ± SEM) of ~50 wild-type flies in (A) 12:12 light-dark (LD) and (B) constant darkness (DD) conditions, as a function of time. In (A) red arrows indicate the morning and evening anticipatory activities; ZT: Zeitgeber Time. In (B) CT: Circadian Time; (C) Schematic representation of the adult fly brain, in which the relative positions of the circadian neurons (right), the dopaminergic neurons (left), the mushroom bodies (MB), the central complex (CC), the Pars Intercerebralis (PI) are reported. Right hemisphere: lLNv: large ventral lateral neurons; sLNv: small LNvs; 5th sLNv: the fifth PDF-negative sLNv; LPN: lateral posterior neuron; LNd: dorsal LNs; DN1: dorsal neurons group 1; DN2: DN group 2; DN3: DN group 3; ey: relative position of the compound eye. Left hemisphere: PAM: Protocerebral Anterior Medial group; PAL: Protocerebral Anterior Lateral group; PPM1-4: Protocerebral Posterior Medial groups 1–4; PPL1–5: Protocerebral Posterior Lateral groups 1–5; VUM: Ventral Unpaired Median group; open circles in the left optic lobe indicate the TH positive cells of the medulla. (D) The two major TTLs of the circadian molecular clock in Drosophila. In the first Drosophila TTL, dCLK and dCYC form a dimer which binds the Enhancer boxes (E-boxes) in the promoter of the dper and dtim clock genes. dPER and dTIM proteins interact to form a complex, enter into the nucleus, and inhibit dCLK-dCYC activity. A second TTL modulates dClk expression: the dCLK-dCYC dimer induces the transcription of dvri and dPdp1 δ/ε genes. dVRI and dPDP1 δ/ε compete for the same element (D-box) in the dClk promoter, controlling dClk transcription. Post-translational modifications mediated by the kinases dDBT and dSGG modulate clock protein activities, regulating protein–protein interactions, nuclear translocation and degradation. In some clock neurons, light activates the internal photoreceptor dCRY which associates with dTIM and mediates its degradation. CLOCK: Circadian Locomotor Output Cycles Kaput; CRY: Cryptochrome; CYC: Cycle; PER: Period; TIM: Timeless; VRI: Vrille; PDP1: Par Domain Protein 1; DBT: Doubletime; SGG: Shaggy. Black arrows indicate the flow of the process; black sinusoidal lines and red arrows indicate transcriptional activity; blue arrows indicate the protein translation process (A,B) Graphs derived from data from our laboratory; (C,D) Modified from [54].