RESUMEN
Thermosensation is critical for the survival of animals. However, mechanisms through which nutritional status modulates thermosensation remain unclear. Herein, we showed that hungry Drosophila exhibit a strong hot avoidance behavior (HAB) compared to food-sated flies. We identified that hot stimulus increases the activity of α'ß' mushroom body neurons (MBns), with weak activity in the sated state and strong activity in the hungry state. Furthermore, we showed that α'ß' MBn receives the same level of hot input from the mALT projection neurons via cholinergic transmission in sated and hungry states. Differences in α'ß' MBn activity between food-sated and hungry flies following heat stimuli are regulated by distinct Drosophila insulin-like peptides (Dilps). Dilp2 is secreted by insulin-producing cells (IPCs) and regulates HAB during satiety, whereas Dilp6 is secreted by the fat body and regulates HAB during the hungry state. We observed that Dilp2 induces PI3K/AKT signaling, whereas Dilp6 induces Ras/ERK signaling in α'ß' MBn to regulate HAB in different feeding conditions. Finally, we showed that the 2 α'ß'-related MB output neurons (MBONs), MBON-α'3 and MBON-ß'1, are necessary for the output of integrated hot avoidance information from α'ß' MBn. Our results demonstrate the presence of dual insulin modulation pathways in α'ß' MBn, which are important for suitable behavioral responses in Drosophila during thermoregulation under different feeding states.
Asunto(s)
Proteínas de Drosophila , Animales , Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Insulina/metabolismo , Cuerpos Pedunculados/fisiología , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de SeñalRESUMEN
The nervous and endocrine systems coordinate with each other to closely influence physiological and behavioural responses in animals. Here we show that WAKE (encoded by wide awake, also known as wake) modulates membrane levels of GABAA receptor Resistance to Dieldrin (Rdl), in insulin-producing cells of adult male Drosophila melanogaster. This results in changes to secretion of insulin-like peptides which is associated with changes in juvenile hormone biosynthesis in the corpus allatum, which in turn leads to a decrease in 20-hydroxyecdysone levels. A reduction in ecdysone signalling changes neural architecture and lowers the perception of the male-specific sex pheromone 11-cis-vaccenyl acetate by odorant receptor 67d olfactory neurons. These finding explain why WAKE-deficient in Drosophila elicits significant male-male courtship behaviour.
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Proteínas de Drosophila , Insulinas , Acetatos , Animales , Cortejo , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Sistema Endocrino/metabolismo , Masculino , Percepción , Feromonas , Receptores de GABA-A , Conducta Sexual Animal/fisiologíaRESUMEN
Memory consolidation is a time-dependent process through which an unstable learned experience is transformed into a stable long-term memory; however, the circuit and molecular mechanisms underlying this process are poorly understood. The Drosophila mushroom body (MB) is a huge brain neuropil that plays a crucial role in olfactory memory. The MB neurons can be generally classified into three subsets: γ, αß, and α'ß'. Here, we report that water-reward long-term memory (wLTM) consolidation requires activity from α'ß'-related mushroom body output neurons (MBONs) in a specific time window. wLTM consolidation requires neurotransmission in MBON-γ3ß'1 during the 0-2 h period after training, and neurotransmission in MBON-α'2 is required during the 2-4 h period after training. Moreover, neurotransmission in MBON-α'1α'3 is required during the 0-4 h period after training. Intriguingly, blocking neurotransmission during consolidation or inhibiting serotonin biosynthesis in serotoninergic dorsal paired medial (DPM) neurons also disrupted the wLTM, suggesting that wLTM consolidation requires serotonin signals from DPM neurons. The GFP Reconstitution Across Synaptic Partners (GRASP) data showed the connectivity between DPM neurons and MBON-γ3ß'1, MBON-α'2, and MBON-α'1α'3, and RNAi-mediated silencing of serotonin receptors in MBON-γ3ß'1, MBON-α'2, or MBON-α'1α'3 disrupted wLTM. Taken together, our results suggest that serotonin released from DPM neurons modulates neuronal activity in MBON-γ3ß'1, MBON-α'2, and MBON-α'1α'3 at specific time windows, which is critical for the consolidation of wLTM in Drosophila.
RESUMEN
Forms of lead (Pb) have been insidiously invading human life for thousands of years without obvious signs of their considerable danger to human health. Blood lead level (BLL) is the routine measure used for diagnosing the degree of lead intoxication, although it is unclear whether there is any safe range of BLL. To develop a practical detection tool for living organisms, we engineered a genetically encoded fluorescence resonance energy transfer (FRET)-based Pb2+ biosensor, 'Met-lead 1.44 M1', with excellent performance. Met-lead 1.44 M1 has an apparent dissociation constant (Kd) of 25.97 nM, a detection limit (LOD) of 10 nM (2.0 ppb/0.2 µg/dL), and an enhancement dynamic ratio of nearly ~ 5-fold upon Pb2+ binding. The 10 nM sensitivity of Met-lead 1.44 M1 is five times below the World Health Organization-permitted level of lead in tap water (10 ppb; WHO, 2017), and fifteen times lower than the maximum BLL for children (3 µg/dL). We deployed Met-lead 1.44 M1 to measure Pb2+ concentrations in different living models, including two general human cell lines and one specific line, induced pluripotent stem cell (iPSC)-derived cardiomyocytes, as well as in widely used model species in plant (Arabidopsis thaliana) and animal (Drosophila melanogaster) research. Our results suggest that this new biosensor is suitable for lead toxicological research in vitro and in vivo, and will pave the way toward potential applications for both low BLL measures and rapid detection of environmental lead in its divalent form.
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Técnicas Biosensibles , Plomo , Animales , Drosophila melanogaster , Transferencia Resonante de Energía de Fluorescencia , Plomo/toxicidadRESUMEN
Long-term memory (LTM) formation depends on the conversed cAMP response element-binding protein (CREB)-dependent gene transcription followed by de novo protein synthesis. Thirsty fruit flies can be trained to associate an odor with water reward to form water-reward LTM (wLTM), which can last for over 24 hours without a significant decline. The role of de novo protein synthesis and CREB-regulated gene expression changes in neural circuits that contribute to wLTM remains unclear. Here, we show that acute inhibition of protein synthesis in the mushroom body (MB) αß or γ neurons during memory formation using a cold-sensitive ribosome-inactivating toxin disrupts wLTM. Furthermore, adult stage-specific expression of dCREB2b in αß or γ neurons also disrupts wLTM. The MB αß and γ neurons can be further classified into five different neuronal subsets including αß core, αß surface, αß posterior, γ main, and γ dorsal. We observed that the neurotransmission from αß surface and γ dorsal neuron subsets is required for wLTM retrieval, whereas the αß core, αß posterior, and γ main are dispensable. Adult stage-specific expression of dCREB2b in αß surface and γ dorsal neurons inhibits wLTM formation. In vivo calcium imaging revealed that αß surface and γ dorsal neurons form wLTM traces with different dynamic properties, and these memory traces are abolished by dCREB2b expression. Our results suggest that a small population of neurons within the MB circuits support long-term storage of water-reward memory in Drosophila.
Asunto(s)
Proteína de Unión a Elemento de Respuesta al AMP Cíclico/genética , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Memoria a Largo Plazo/fisiología , Neuronas/metabolismo , Olfato/genética , Transactivadores/genética , Animales , Animales Modificados Genéticamente , Calcio/metabolismo , Drosophila melanogaster/fisiología , Cuerpos Pedunculados/fisiología , Neuronas/fisiología , Biosíntesis de Proteínas/genética , Recompensa , Olfato/fisiología , Transmisión Sináptica/genética , AguaRESUMEN
The harmful impact of the heavy metal lead on human health has been known for years. However, materials that contain lead remain in the environment. Measuring the blood lead level (BLL) is the only way to officially evaluate the degree of exposure to lead. The so-called "safe value" of the BLL seems to unreliably represent the secure threshold for children. In general, lead's underlying toxicological mechanism remains unclear and needs to be elucidated. Therefore, we developed a novel genetically encoded fluorescence resonance energy transfer (FRET)-based lead biosensor, Met-lead, and applied it to transgenic Drosophila to perform further investigations. We combined Met-lead with the UAS-GAL4 system to the sensor protein specifically expressed within certain regions of fly brains. Using a suitable imaging platform, including a fast epifluorescent or confocal laser-scanning/two-photon microscope with high resolution, we recorded the changes in lead content inside fly brains ex vivo and in vivo and at different life stages. The blood-brain barrier was found to play an important role in the protection of neurons in the brain against damage due to the heavy metal lead, either through food or microinjection into the abdomen. Met-lead has the potential to be a powerful tool for the sensing of lead within living organisms by employing either a fast epi-FRET microscope or high-resolution brain imaging.
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Técnicas Biosensibles , Drosophila melanogaster/química , Plomo/aislamiento & purificación , Metales Pesados/aislamiento & purificación , Animales , Plomo/química , Metales Pesados/químicaRESUMEN
Electrical synapses between neurons, also known as gap junctions, are direct cell membrane channels between adjacent neurons. Gap junctions play a role in the synchronization of neuronal network activity; however, their involvement in cognition has not been well characterized. Three-hour olfactory associative memory in Drosophila has two components: consolidated anesthesia-resistant memory (ARM) and labile anesthesia-sensitive memory (ASM). Here, we show that knockdown of the gap junction gene innexin5 (inx5) in mushroom body (MB) neurons disrupted ARM, while leaving ASM intact. Whole-mount brain immunohistochemistry indicated that INX5 protein was preferentially expressed in the somas, calyxes, and lobes regions of the MB neurons. Adult-stage-specific knockdown of inx5 in αß neurons disrupted ARM, suggesting a specific requirement of INX5 in αß neurons for ARM formation. Hyperpolarization of αß neurons during memory retrieval by expressing an engineered halorhodopsin (eNpHR) also disrupted ARM. Administration of the gap junction blocker carbenoxolone (CBX) reduced the proportion of odor responsive αß neurons to the training odor 3 hours after training. Finally, the α-branch-specific 3-hour ARM-specific memory trace was also diminished with CBX treatment and in inx5 knockdown flies. Altogether, our results suggest INX5 gap junction channels in αß neurons for ARM retrieval and also provide a more detailed neuronal mechanism for consolidated memory in Drosophila.
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Conexinas/genética , Sinapsis Eléctricas/fisiología , Cuerpos Pedunculados/metabolismo , Animales , Encéfalo/metabolismo , Carbenoxolona/farmacología , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Sinapsis Eléctricas/metabolismo , Uniones Comunicantes/metabolismo , Uniones Comunicantes/fisiología , Memoria/fisiología , Cuerpos Pedunculados/fisiología , Neuronas/metabolismo , Odorantes , Olfato/genética , Transmisión Sináptica/fisiologíaRESUMEN
Dietary restriction (DR; sometimes called calorie restriction) has profound beneficial effects on physiological, psychological, and behavioral outcomes in animals and in humans. We have explored the molecular mechanism of DR-induced memory enhancement and demonstrate that dietary tryptophan-a precursor amino acid for serotonin biosynthesis in the brain-and serotonin receptor 5-hydroxytryptamine receptor 6 (HTR6) are crucial in mediating this process. We show that HTR6 inactivation diminishes DR-induced neurological alterations, including reduced dendritic complexity, increased spine density, and enhanced long-term potentiation (LTP) in hippocampal neurons. Moreover, we find that HTR6-mediated mechanistic target of rapamycin complex 1 (mTORC1) signaling is involved in DR-induced memory improvement. Our results suggest that the HTR6-mediated mTORC1 pathway may function as a nutrient sensor in hippocampal neurons to couple memory performance to dietary intake.
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Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Memoria/fisiología , Receptores de Serotonina/metabolismo , Ácido 3-Hidroxibutírico/sangre , Animales , Western Blotting , Corticosterona/sangre , Electrofisiología , Prueba de Tolerancia a la Glucosa , Hipocampo/citología , Hipocampo/metabolismo , Potenciación a Largo Plazo/fisiología , Masculino , Diana Mecanicista del Complejo 1 de la Rapamicina/genética , Ratones , Ratones Endogámicos C57BL , Neuronas/citología , Neuronas/metabolismo , ARN Mensajero/metabolismo , Receptores de Serotonina/genética , Serotonina/sangre , Transducción de Señal/genética , Transducción de Señal/fisiologíaRESUMEN
Appropriate sexual selection or individual sexual attractiveness is closely associated with the reproductive success of a species. Here, we report that young male flies exhibit innate courtship preference for female flies that are raised on higher-yeast diets and that have greater body weight and fecundity, but reduced locomotor activity and shortened lifespan. Male flies discriminate among females that have been fed diets that contain 3 different yeast concentrations-1, 5, and 20% yeast- via gustatory, but not visual or olfactory, perception. Female flies that are raised on higher-yeast diets exhibit elevated expression levels of Drosophila insulin-like peptides (di lps), and we demonstrate that hypomorphic mutations of di lp2, 3, 5 or foxo, as well as oenocyte-specific gene disruption of the insulin receptor, all abolish this male courtship preference for high yeast-fed females. Moreover, our data demonstrate that disrupted di lp signaling can alter the expression profile of some cuticular hydrocarbons (CHCs) in female flies, and that genetic inhibition of an enzyme involved in the biosynthesis of CHCs in oenocytes, elongase F, also eliminates the male courtship preference. Together, our findings provide mechanistic insights that link female reproductive potential to sexual attractiveness, thereby encouraging adaptive mating and optimal reproductive success.-Lin, W.-S., Yeh, S.-R., Fan, S.-Z., Chen, L.-Y., Yen, J.-H., Fu, T.-F., Wu, M.-S., Wang, P.-Y. Insulin signaling in female Drosophila links diet and sexual attractiveness.
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Dieta , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Preferencia en el Apareamiento Animal , Animales , Proteínas de Drosophila/genética , Drosophila melanogaster/fisiología , Femenino , Péptidos y Proteínas de Señalización Intercelular/genética , Masculino , Transducción de SeñalRESUMEN
The intake of water is important for the survival of all animals and drinking water can be used as a reward in thirsty animals. Here we found that thirsty Drosophila melanogaster can associate drinking water with an odour to form a protein-synthesis-dependent water-reward long-term memory (LTM). Furthermore, we found that the reinforcement of LTM requires water-responsive dopaminergic neurons projecting to the restricted region of mushroom body (MB) ß' lobe, which are different from the neurons required for the reinforcement of learning and short-term memory (STM). Synaptic output from α'ß' neurons is required for consolidation, whereas the output from γ and αß neurons is required for the retrieval of LTM. Finally, two types of MB efferent neurons retrieve LTM from γ and αß neurons by releasing glutamate and acetylcholine, respectively. Our results therefore cast light on the cellular and molecular mechanisms responsible for processing water-reward LTM in Drosophila.
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Ingestión de Líquidos/fisiología , Drosophila melanogaster/fisiología , Memoria a Largo Plazo/fisiología , Red Nerviosa/fisiología , Recompensa , Acetilcolina/metabolismo , Animales , Animales Modificados Genéticamente , Conducta Animal/fisiología , Condicionamiento Clásico , Neuronas Dopaminérgicas/fisiología , Proteínas de Drosophila/biosíntesis , Ácido Glutámico/metabolismo , Memoria a Corto Plazo/fisiología , Cuerpos Pedunculados/fisiología , Neuronas Eferentes/fisiología , Odorantes , Refuerzo en Psicología , Olfato/fisiologíaRESUMEN
The neurology of male sexuality has been poorly studied owing to difficulties in studying brain circuitry in humans. Dopamine (DA) is essential for both physiological and behavioural responses, including the regulation of sexuality. Previous studies have revealed that alterations in DA synthesis in dopaminergic neurons can induce male-male courtship behaviour, while increasing DA levels in the protocerebral posteriolateral dopaminergic cluster neuron 2ab (PPL2ab) may enhance the intensity of male courtship sustainment in Drosophila. Here we report that changes in the ability of the PPL2ab in the central nervous system (CNS) to produce DA strongly impact male-male courtship in D. melanogaster. Intriguingly, the DA-synthesizing abilities of these neurons appear to affect both the courting activities displayed by male flies and the sex appeal of male flies for other male flies. Moreover, the observed male-male courtship is triggered primarily by target motion, yet chemical cues can replace visual input under dark conditions. This is interesting evidence that courtship responses in male individuals are controlled by PPL2ab neurons in the CNS. Our study provides insight for subsequent studies focusing on sexual circuit modulation by PPL2ab neurons.
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Dopamina/metabolismo , Neuronas Dopaminérgicas/metabolismo , Drosophila melanogaster/fisiología , Conducta Sexual Animal/fisiología , Animales , Sistema Nervioso Central/metabolismo , Sistema Nervioso Central/fisiología , Cortejo , Neuronas Dopaminérgicas/fisiología , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Masculino , Sexualidad/fisiologíaRESUMEN
Associative olfactory memory in Drosophila has two components called labile anesthesia-sensitive memory and consolidated anesthesia-resistant memory (ARM). Mushroom body (MB) is a brain region critical for the olfactory memory and comprised of 2000 neurons that can be classified into αß, α'ß', and γ neurons. Previously we demonstrated that two parallel pathways mediated ARM consolidation: the serotonergic dorsal paired medial (DPM)-αß neurons and the octopaminergic anterior paired lateral (APL)-α'ß' neurons. This finding prompted us to ask how this composite ARM is retrieved. Here, we showed that blocking the output of αß neurons and that of α'ß' neurons each impaired ARM retrieval, and blocking both simultaneously had an additive effect. Knockdown of radish and octß2R in αß and α'ß' neurons, respectively, impaired ARM. A combinatorial assay of radish mutant background rsh1 and neurotransmission blockade confirmed that ARM retrieved from α'ß' neuron output is independent of radish. We identified MBON-ß2ß'2a and MBON-ß'2mp as the MB output neurons downstream of αß and α'ß' neurons, respectively, whose glutamatergic transmissions also additively contribute to ARM retrieval. Finally, we showed that α'ß' neurons could be functionally subdivided into α'ß'm neurons required for ARM retrieval, and α'ß'ap neurons required for ARM consolidation. Our work demonstrated that two parallel neural pathways mediating ARM consolidation in Drosophila MB additively contribute to ARM expression during retrieval.
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Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Corteza Olfatoria/metabolismo , Fosfoproteínas/genética , Receptores Acoplados a Proteínas G/genética , Olfato/genética , Anestesia/efectos adversos , Animales , Animales Modificados Genéticamente , Drosophila melanogaster/metabolismo , Técnicas de Silenciamiento del Gen , Memoria/efectos de los fármacos , Cuerpos Pedunculados/efectos de los fármacos , Cuerpos Pedunculados/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Olfato/fisiología , Transmisión Sináptica/efectos de los fármacos , Transmisión Sináptica/genéticaRESUMEN
The possible neurological and biophysical effects of magnetic fields on animals is an area of active study. Here, we report that courtship activity of male Drosophila increases in a magnetic field and that this effect is regulated by the blue light-dependent photoreceptor cryptochrome (CRY). Naïve male flies exhibited significantly increased courtship activities when they were exposed to a ≥ 20-Gauss static magnetic field, compared with their behavior in the natural environment (0 Gauss). CRY-deficient flies, cryb and crym, did not show an increased courtship index in a magnetic field. RNAi-mediated knockdown of cry in cry-GAL4-positive neurons disrupted the increased male courtship activity in a magnetic field. Genetically expressing cry under the control of cry-GAL4 in the CRY-deficient flies restored the increase in male courtship index that occurred in a magnetic field. Interestingly, artificially activating cry-GAL4-expressing neurons, which include large ventral lateral neurons and small ventral lateral neurons, via expression of thermosensitive cation channel dTrpA1, also increased the male courtship index. This enhancement was abolished by the addition of the cry-GAL80 transgene. Our results highlight the phenomenon of increased male courtship activity caused by a magnetic field through CRY-dependent magnetic sensation in CRY expression neurons in Drosophila.
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Criptocromos/genética , Drosophila/fisiología , Campos Magnéticos , Conducta Sexual Animal , Animales , Drosophila/genética , Drosophila/metabolismo , Proteínas de Drosophila/genética , Canales Iónicos , Canal Catiónico TRPA1 , Canales Catiónicos TRPC/genéticaRESUMEN
OBJECTIVE: To study clinical factors predicting the absence of endocervical/transformation zone (EC/TZ) components of conventional cervical Papanicolaou (Pap) smears. MATERIALS AND METHODS: The medical charts of patients who received Pap smears between March 2006 and August 2006 in the hospital were reviewed. The results of their Pap smears were retrieved while their demographic and clinical information were obtained from the medical charts. After excluding 378 cases with incomplete demographic data and 1397 cases with a history of pelvic irradiation, pelvic malignancy, and hysterectomy, 5662 cases were enrolled for data analysis. The relationship between clinical parameters and the absence of EC/TZ component was analyzed by Pearson Chi-square tests with Yates continuity correction and binary logistic regression tests. RESULTS: The incidence of satisfactory but absence of EC/TZ component was 8.7% (491/5662). Pregnancy increased the absence of EC/TZ component [odds ratio (OR}: 2.84, 95% confidence interval (CI): 2.14-3.77, p<0.0001]. Postpartum status and endocervical polyps decreased incidence (OR: 0.61, 95% CI: 0.38-0.98, p = 0.043 and OR: 0.33, 95% CI: 0.25-0.44, p<0.0001, respectively). CONCLUSIONS: Pregnancy is the only clinical factor associated with increased incidence of absence of EC/TZ cells. For these pregnant women undergoing a Pap smear, a more effective strategy may be needed to get a satisfactory smear with adequate EC/TZ components.
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Cuello del Útero/patología , Prueba de Papanicolaou/normas , Pólipos/complicaciones , Indicadores de Calidad de la Atención de Salud , Enfermedades del Cuello del Útero/complicaciones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Persona de Mediana Edad , Periodo Posparto , Embarazo , Adulto JovenRESUMEN
In order to identify genes involved in stress and metabolic regulation, we carried out a Drosophila P-element-mediated mutagenesis screen for starvation resistance. We isolated a mutant, m2, that showed a 23% increase in survival time under starvation conditions. The P-element insertion was mapped to the region upstream of the vha16-1 gene, which encodes the c subunit of the vacuolar-type H+-ATPase. We found that vha16-1 is highly expressed in the fly midgut, and that m2 mutant flies are hypomorphic for vha16-1 and also exhibit reduced midgut acidity. This deficit is likely to induce altered metabolism and contribute to accelerated aging, since vha16-1 mutant flies are short-lived and display increases in body weight and lipid accumulation. Similar phenotypes were also induced by pharmacological treatment, through feeding normal flies and mice with a carbonic anhydrase inhibitor (acetazolamide) or proton pump inhibitor (PPI, lansoprazole) to suppress gut acid production. Our study may thus provide a useful model for investigating chronic acid suppression in patients.
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Equilibrio Ácido-Base/genética , Proteínas de Drosophila/genética , Tracto Gastrointestinal/metabolismo , Obesidad/genética , Fenotipo , ATPasas de Translocación de Protón Vacuolares/genética , Acetazolamida/farmacología , Animales , Inhibidores de Anhidrasa Carbónica/farmacología , Proteínas de Drosophila/metabolismo , Drosophila melanogaster , Determinación de la Acidez Gástrica , Tracto Gastrointestinal/efectos de los fármacos , Lansoprazol/farmacología , Ratones , Obesidad/metabolismo , Inhibidores de la Bomba de Protones/farmacología , ATPasas de Translocación de Protón Vacuolares/metabolismoRESUMEN
The aging process is a universal phenomenon shared by all living organisms. The identification of longevity genes is important in that the study of these genes is likely to yield significant insights into human senescence. In this study, we have identified Tequila as a novel candidate gene involved in the regulation of longevity in Drosophila melanogaster. We have found that a hypomorphic mutation of Tequila (Teq(f01792)), as well as cell-specific downregulation of Tequila in insulin-producing neurons of the fly, significantly extends life span. Tequila deficiency-induced life-span extension is likely to be associated with reduced insulin-like signaling, because Tequila mutant flies display several common phenotypes of insulin dysregulation, including reduced circulating Drosophila insulin-like peptide 2 (Dilp2), reduced Akt phosphorylation, reduced body size, and altered glucose homeostasis. These observations suggest that Tequila may confer life-span extension by acting as a modulator of Drosophila insulin-like signaling.
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Proteínas de Drosophila/fisiología , Drosophila melanogaster/fisiología , Insulina/fisiología , Péptidos y Proteínas de Señalización Intercelular/fisiología , Longevidad/fisiología , Serina Endopeptidasas/fisiología , Transducción de Señal/fisiología , Animales , Femenino , Esperanza de Vida , MasculinoRESUMEN
The detection of environmental temperature and regulation of body temperature are integral determinants of behaviour for all animals. These functions become less efficient in aged animals, particularly during exposure to cold environments, yet the cellular and molecular mechanisms are not well understood. Here, we identify an age-related change in the temperature preference of adult fruit flies that results from a shift in the relative contributions of two parallel mushroom body (MB) circuitsthe ß'- and ß-systems. The ß'-circuit primarily controls cold avoidance through dopamine signalling in young flies, whereas the ß-circuit increasingly contributes to cold avoidance as adult flies age. Elevating dopamine levels in ß'-afferent neurons of aged flies restores cold sensitivity, suggesting that the alteration of cold avoidance behaviour with ageing is functionally reversible. These results provide a framework for investigating how molecules and individual neural circuits modulate homeostatic alterations during the course of senescence.
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Envejecimiento/fisiología , Conducta Animal/fisiología , Regulación de la Temperatura Corporal/fisiología , Conducta de Elección/fisiología , Dopamina/metabolismo , Cuerpos Pedunculados/metabolismo , Neuronas/metabolismo , Receptores Dopaminérgicos/metabolismo , Temperatura , Animales , Reacción de Prevención/fisiología , Calcio/metabolismo , Frío , Drosophila melanogaster , Cuerpos Pedunculados/citologíaRESUMEN
Male sexual desire typically declines with ageing. However, our understanding of the neurobiological basis for this phenomenon is limited by our knowledge of the brain circuitry and neuronal pathways controlling male sexual desire. A number of studies across species suggest that dopamine (DA) affects sexual desire. Here we use genetic tools and behavioural assays to identify a novel subset of DA neurons that regulate age-associated male courtship activity in Drosophila. We find that increasing DA levels in a subset of cells in the PPL2ab neuronal cluster is necessary and sufficient for increased sustained courtship in both young and aged male flies. Our results indicate that preventing the age-related decline in DA levels in PPL2ab neurons alleviates diminished courtship behaviours in male Drosophila. These results may provide the foundation for deciphering the circuitry involved in sexual motivation in the male Drosophila brain.
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Envejecimiento/fisiología , Dopamina/metabolismo , Neuronas Dopaminérgicas/fisiología , Drosophila/fisiología , Conducta Sexual Animal/fisiología , Animales , Dopamina/genética , MasculinoRESUMEN
Animals have to judge environmental cues and choose the most suitable option for them from many different options. Female fruit flies selecting an optimum site to deposit their eggs is a biologically important reproductive behavior. When given the direct choice between ovipositing their eggs in a sucrose-containing medium or a caffeine-containing medium, female flies prefer the latter. However, the neural circuits and molecules that regulate this decision-making processes during egg-laying site selection remain poorly understood. In the present study, we found that amnesiac (amn) mutant flies show significant defects in egg-laying decisions, and such defects can be reversed by expressing the wild-type amn transgene in two dorsal paired medial (DPM) neurons in the brain. Silencing neuronal activity with an inward rectifier potassium channel (Kir2.1) in DPM neurons also impairs egg-laying decisions. Finally, the activity in mushroom body αß neurons is required for the egg-laying behavior, suggesting a possible "DPM-αß neurons" brain circuit modulating egg-laying decisions. Our results highlight the brain circuits and molecular mechanisms of egg-laying decisions in Drosophila.
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Neuronas/fisiología , Oviposición/fisiología , Conducta Sexual Animal/fisiología , Animales , Cafeína/farmacología , Drosophila melanogaster , Femenino , Oviposición/efectos de los fármacos , Canales de Potasio de Rectificación Interna/genética , Canales de Potasio de Rectificación Interna/metabolismo , Conducta Sexual Animal/efectos de los fármacos , Sacarosa/farmacologíaRESUMEN
Local neurons in the vertebrate retina are instrumental in transforming visual inputs to extract contrast, motion, and color information and in shaping bipolar-to-ganglion cell transmission to the brain. In Drosophila, UV vision is represented by R7 inner photoreceptor neurons that project to the medulla M6 stratum, with relatively little known of this downstream substrate. Here, using R7 terminals as references, we generated a 3D volume model of the M6 stratum, which revealed a retinotopic map for UV representations. Using this volume model as a common 3D framework, we compiled and analyzed the spatial distributions of more than 200 single M6-specific local neurons (M6-LNs). Based on the segregation of putative dendrites and axons, these local neurons were classified into two families, directional and nondirectional. Neurotransmitter immunostaining suggested a signal routing model in which some visual information is relayed by directional M6-LNs from the anterior to the posterior M6 and all visual information is inhibited by a diverse population of nondirectional M6-LNs covering the entire M6 stratum. Our findings suggest that the Drosophila medulla M6 stratum contains diverse LNs that form repeating functional modules similar to those found in the vertebrate inner plexiform layer.