A role for Notch in the elaboration of existing neural processes is emerging that is distinct from the increasingly well understood function of this gene in binary cell-fate decisions. Several research groups, by using a variety of organisms, have shown that Notch is important in the development of neural ultrastructure. Simultaneously, Presenilin (Psn) was identified both as a key mediator of Notch signaling and as a site of genetic lesions that cause earlyonset Alzheimer's disease. Here we demonstrate that Notch loss of function produces memory deficits in Drosophila melanogaster. The effects are specific to long-term memory, which is thought to depend on ultrastructural remodeling. We propose that Notch plays an important role in the neural plasticity underlying consolidated memory.W hereas the Notch protein plays an important role in binary cell-fate decisions during development (1), it is also present in the adult brain (2, 3). This finding is particularly interesting in adult Drosophila because the CNS is established by eclosion (4). Given that Notch is not needed for cell-fate decisions in the adult brain, its role in this tissue is unclear.Several groups have shown that Notch is important in the arborization of neuritic processes in development. In mammals, Notch regulates arborization of cortical neurons in vivo (5, 6) and in tissue culture (7,8). In Drosophila, the Notch pathway is required for the elaboration of processes in the CNS in the developing third-instar larva (9) and in the embryo (10, 11). Recently, this work has been extended to the analysis of the developing neuromuscular junction, a structure that serves as an accessible model for CNS plasticity. In addition, a Psn-mediated role for Notch is required in the development of neural projections mediating learned thermotaxis in Caenorhabditis elegans (12). Recently (3), we demonstrated that prolonged disruptions in Notch function produced an early lethality and an impairment in the coordinated neuromuscular activity of flight. Accordingly, because Notch clearly is involved in the regulation of neural ultrastructure during development, we investigated the possibility that Notch is also required for memory consolidation, a process believed to require remodeling of existing neurons in adults (13).Drosophila is an ideal organism for studying genes influencing behavioral phenotypes. Advances in our understanding of learning and memory mechanisms have been achieved through genetic, transgenic, and genomic studies in the fly (14). To investigate Notch function in adults, it is necessary to use conditional reagents to avoid developmental phenotypes that may kill the fly or compromise behavior. We used a Notch temperature-sensitive allele (N ts1 ) (15) and RNA interference (RNAi) derived from an inducible transgene (16), in combination with two independent behavioral assays for memory. We show that short-term memory is not impaired by conditional manipulations of Notch, but that Notch is required in adults for long-term memory. MethodsDrosophila Strai...
The central body (or central complex, CCX) and the mushroom bodies (MBs) are brain structures in most insect phyla that have been shown to influence aspects of locomotion. The CCX regulates motor coordination and enhances activity while MBs have, thus far, been shown to suppress motor activity levels measured over time intervals ranging from hours to weeks. In this report, we investigate MB involvement in motor behavior during the initial stages (15 minutes) of walking in Buridan's paradigm. We measured aspects of walking in flies that had MB lesions induced by mutations in six different genes and by chemical ablation. All tested flies were later examined histologically to assess MB neuroanatomy. Mutant strains with MB structural defects were generally less active in walking than wild-type flies. Most mutants in which MBs were also ablated with hydroxyurea (HU) showed additional activity decrements. Variation in measures of velocity and orientation to landmarks among wild-type and mutant flies was attributed to pleiotropy, rather than to MB lesions. We conclude that MBs upregulate activity during the initial stages of walking, but suppress activity thereafter. An MB influence on decision making has been shown in a wide range of complex behaviors. We suggest that MBs provide appropriate contextual information to motor output systems in the brain, indirectly fine tuning walking by modifying the quantity (i.e., activity) of behavior.
Summary Storage and release of classical and amino acid neurotransmitters requires vesicular transporters. Some neurons lack known vesicular transporters, suggesting additional neurotransmitter systems remain unidentified. Insect mushroom bodies (MBs) are critical for several behaviors, including learning, but the neurotransmitters released by the intrinsic Kenyon cells (KCs) remain unknown. Likewise, KCs do not express a known vesicular transporter. We report the identification of a novel Drosophila gene portabella (prt) that is structurally similar to known vesicular transporters. Both larval and adult brains express PRT in the KCs of the MBs. Additional PRT cells project to the central complex and optic ganglia. prt mutation causes an olfactory learning deficit and an unusual defect in the male’s position during copulation that is rescued by expression in KCs. Since prt is expressed in neurons that lack other known vesicular transporters or neurotransmitters, it may define a previously unknown neurotransmitter system responsible for sexual behavior and a component of olfactory learning.
Cellular transport and memory consolidation in Drosophila mushroom bodies 2 Table S1. Fly strains used in this study. Genotype Symbol Description Source Canton Special wü CS wild-type Heisenberg Berlin B wild-type Heisenberg w 1118 (CS) w w in CS background this lab 2 mbmB 1 (CS)/SM5 mbmB MB mutant in CS background this lab 1 w; mbmB 1 (CS)/SM5 w; mbmB MB mutant in w(CS) background this lab 1 y w; imp-α2 D14 /y + CyO; TM6 D14 Imp-α2 null mutant Mechler 3 Balancer In(1)FM7a B 1 w a y 31d FM7a chromosome-1 this lab 1,2 w; al Bl/In(2LR)SM5, Duox Cy al 2 w; al Bl/SM5 chromosome-2 this lab 2 w; TM3 Ubx bx-34e e 1 /TM6b Antp Hu e 1 w; TM3/TM6b chromosome-3 this lab 2 Deficiency & P-element 4 Cytology | Sequence w; Df(2L)γ7/CyO
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