Figure 1.

Key centers of the mammalian and Drosophila brains and the circadian system in Drosophila. (A) Some of the key areas of the human brain involved in the control of arousal/sleep, circadian rhythms, and cognitive processes related to motivation, emotions, and learning/memory. Hippocampus (HP): this relatively large structure is part of the limbic system and is involved in stabilizing information in the consolidation of short-term to long-term memory. The HP is also implicated in spatial navigation. Locus coeruleus (LC): norepinephrine from the LC mediates arousal, and primes the brain’s neurons to be activated by stimuli, and is involved with physiological responses to stress and panic. Nucleus accumbens (NA): this region of the brain is involved in the cognitive elaboration of associative learning, motivation, pleasure, and addiction/reward. Orexinergic neurons (ORX): these neurons produce the neurotransmitter orexin/hypocretin, which is involved in regulating arousal, wakefulness, and appetite. Suprachiasmatic nucleus (SCN): these neurons are situated directly above the optic chiasm and are the seat of the central clock (yellow), which controls circadian rhythms through the action of different peptides and neurotransmitters on many other regions of the brain, which contain subsidiary clocks (white). Raphe nuclei (RN): these serotoninergic nuclei are involved in a reciprocal feedback loop with the SCN to which they send information regarding levels of alertness; the SCN in turn sends connections to the RN; thus, influencing serotonin levels, which are involved in regulating sleep/wake states. Ventrotegmental area (VTA): the dopaminergic neurons of this area of the brain are involved in cognitive processes related to addiction/reward and motivation. Tuberomammillary nuclei (TMN): these histaminergic nuclei are involved in the control of arousal, learning, memory, sleep, and energy balance. Retinohypothalamic tract (RHT): the retinohypothalamic tract originates in the intrinsically photosensitive retinal ganglion cells, which contain the photopigment melanopsin. The RHT axons, through the optic nerve and the optic chiasm, project to the suprachiasmatic nuclei. Ventrolateral preoptic nucleus (VLPO): the VLPO is active during sleep and releases mainly GABA and galanin, which inhibit neurons that are involved in wakefulness and arousal (i.e., ORX, RN, LC, TMN). The latter groups of neurons are involved in a reciprocal feedback loop with the VLPO, thus contributing to the regulation of sleep. (B) The circadian system organization in Drosophila, with multiple oscillators located in the brain and body. The clocks in the brain, and in most of the peripheral tissues, are autonomous (yellow), while those located in the oenocytes resemble the mammalian subsidiary clocks (white), whose phase is controlled by the central brain clock; see text for details. Upper part: schematic representation of the adult fly brain, in which the relative positions of the circadian neurons, the mushroom bodies (MBs), the central complex (CC), the pars lateralis (PL), and the pars intercelebralis (PI) are reported [modified from Ref. (8, 9)]. The inset shows a 3D-reconstruction of the MBs and CC. KC: kenyon cells; CA: calyx; PED: pedunculus; α: α lobe; α1: α′ lobe; β: β lobe; β1: β′ lobe; γ: γ lobe; EB: ellipsoid body; FB: fan-shaped body; N: noduli; PB: protocerebral bridge; lLNv: large ventral lateral neurons; sLNv: small LNvs; 5th sLNv: the 5th 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 respect to the brain.