Fly Brain Research Articles

Lint‐O cooperates with L(3)mbt in target gene suppression to maintain homeostasis in fly ovary and brain

Loss‐of‐function mutations in Drosophila lethal(3)malignant brain tumor [l(3)mbt] cause ectopic expression of germline genes and brain tumors. Loss of L(3)mbt function in ovarian somatic cells (OSCs) aberrantly activates germ‐specific piRNA amplification and leads to infertility. However, the underlying mechanism remains unclear. Here, ChIP‐seq for L(3)mbt in cultured OSCs and RNA‐seq before and after L(3)mbt depletion shows that L(3)mbt genomic binding is not necessarily linked to gene regulation and that L(3)mbt controls piRNA pathway genes in multiple ways. Lack of known L(3)mbt co‐repressors, such as Lint‐1, has little effect on the levels of piRNA amplifiers. Identification of L(3)mbt interactors in OSCs and subsequent analysis reveals CG2662 as a novel co‐regulator of L(3)mbt, termed “L(3)mbt interactor in OSCs” (Lint‐O). Most of the L(3)mbt‐bound piRNA amplifier genes are also bound by Lint‐O in a similar fashion. Loss of Lint‐O impacts the levels of piRNA amplifiers, similar to the lack of L(3)mbt. The lint‐O‐deficient flies exhibit female sterility and tumorous brains. Thus, L(3)mbt and its novel co‐suppressor Lint‐O cooperate in suppressing target genes to maintain homeostasis in the ovary and brain.

A thermometer circuit for hot temperature adjusts Drosophila behavior to persistent heat

Small poikilotherms such as the fruit fly Drosophila depend on absolute temperature measurements to identify external conditions that are above (hot) or below (cold) their preferred range and to react accordingly. Hot and cold temperatures have a different impact on fly activity and sleep, but the circuits and mechanisms that adjust behavior to specific thermal conditions are not well understood. Here, we use patch-clamp electrophysiology to show that internal thermosensory neurons located within the fly head capsule (the AC neurons1) function as a thermometer active in the hot range. ACs exhibit sustained firing rates that scale with absolute temperature-but only for temperatures above the fly's preferred ∼25°C (i.e., "hot" temperature). We identify ACs in the fly brain connectome and demonstrate that they target a single class of circadian neurons, the LPNs.2 LPNs receive excitatory drive from ACs and respond robustly to hot stimuli, but their responses do not exclusively rely on ACs. Instead, LPNs receive independent drive from thermosensory neurons of the fly antenna via a new class of second-order projection neurons (TPN-IV). Finally, we show that silencing LPNs blocks the restructuring of daytime "siesta" sleep, which normally occurs in response to persistent heat. Our previous work described a distinct thermometer circuit for cold temperature.3 Together, the results demonstrate that the fly nervous system separately encodes and relays absolute hot and cold temperature information, show how patterns of sleep and activity can be adapted to specific temperature conditions, and illustrate how persistent drive from sensory pathways can impact behavior on extended temporal scales.

Dopamine and GPCR-mediated modulation of DN1 clock neurons gates the circadian timing of sleep

The metronome-like circadian regulation of sleep timing must still adapt to an uncertain environment. Recent studies in Drosophila indicate that neuromodulation not only plays a key role in clock neuron synchronization but also affects interactions between the clock network and brain sleep centers. We show here that the targets of neuromodulators, G Protein Coupled Receptors (GPCRs), are highly enriched in the fly brain circadian clock network. Single-cell sequencing indicates that they are not only enriched but also differentially expressed and contribute to clock neuron identity. We generated a comprehensive guide library to mutagenize individual GPCRs in specific neurons and verified the strategy by introducing a targeted sequencing approach. Combined with a behavioral screen, the mutagenesis strategy revealed a role of dopamine in sleep regulation by identifying two dopamine receptors and a clock neuron subpopulation that gate the timing of sleep.

Ageing desexualizes the Drosophila brain transcriptome.

General evolutionary theory predicts that individuals in low condition should invest less in sexual traits compared to individuals in high condition. Whether this positive association between condition and investment also holds between young (high condition) and senesced (low condition) individuals is however less clear, since elevated investment into reproduction may be beneficial when individuals approach the end of their life. To address how investment into sexual traits changes with age, we study genes with sex-biased expression in the brain, the tissue from which sexual behaviours are directed. Across two distinct populations of Drosophila melanogaster, we find that old brains display fewer sex-biased genes, and that expression of both male-biased and female-biased genes converges towards a sexually intermediate phenotype owing to changes in both sexes with age. We further find that sex-biased genes in general show heightened age-dependent expression in comparison to unbiased genes and that age-related changes in the sexual brain transcriptome are commonly larger in males than females. Our results hence show that ageing causes a desexualization of the fruit fly brain transcriptome and that this change mirrors the general prediction that low condition individuals should invest less in sexual phenotypes.

Regulation of sensory perception and motor abilities by brain-specific action of chromatin remodeling factor CHD1.

The ATP-dependent chromatin remodeling factor CHD1 (chromodomain-helicase-DNA binding protein 1) is involved in both the de novo assembly and the remodeling of chromatin. Recently, we discovered a crucial role of CHD1 in the incorporation of the histone variant H3.3 in the fly brain illustrated by widespread transcriptional upregulation and shortened lifespan in Chd1-mutant animals. Because many genes linked to sensory perception were dysregulated in Chd1-mutant heads, we studied the role of CHD1 in these processes. Here we show that Chd1-mutant flies have severe defects in their response behavior to olfactory and gustatory but not visual stimuli. Further analyses suggested that poor performance in gustatory response assays was caused by reduced motivation for foraging and feeding rather than defects in taste perception. Moreover, we show that shortened lifespan of Chd1-mutant flies is accompanied by indications of premature functional aging as suggested by defects in negative geotaxis and exploratory walking assays. The latter phenotype was rescued by neuronal re-expression of Chd1, while the olfactory defects were not. Interestingly, we found evidence for indirect regulation of the non-neuronal expression of odorant binding proteins (Obp) by neuronal expression of Chd1. Together, these results emphasize the crucial role of CHD1 activity controlling diverse neuronal processes thereby affecting healthy lifespan.

How innovations in methodology offer new prospects for volume electron microscopy

Detailed knowledge of biological structure has been key in understanding biology at several levels of organisation, from organs to cells and proteins. Volume electron microscopy (volume EM) provides high resolution 3D structural information about tissues on the nanometre scale. However, the throughput rate of conventional electron microscopes has limited the volume size and number of samples that can be imaged. Recent improvements in methodology are currently driving a revolution in volume EM, making possible the structural imaging of whole organs and small organisms. In turn, these recent developments in image acquisition have created or stressed bottlenecks in other parts of the pipeline, like sample preparation, image analysis and data management. While the progress in image analysis is stunning due to the advent of automatic segmentation and server‐based annotation tools, several challenges remain. Here we discuss recent trends in volume EM, emerging methods for increasing throughput and implications for sample preparation, image analysis and data management.

Imp and Syp mediated temporal patterning of neural stem cells in the developing Drosophila CNS.

The assembly of complex neural circuits requires that stem cells generate diverse types of neurons in the correct temporal order. Pioneering work in the Drosophila embryonic ventral nerve cord has shown that neural stem cells are temporally patterned by the sequential expression of rapidly changing transcription factors to generate diversity in their progeny. In recent years, a second temporal patterning mechanism, driven by the opposing gradients of the Imp and Syp RNA-binding proteins, has emerged as a powerful way to generate neural diversity. This long-range temporal patterning mechanism is utilized in the extended neural stem cell lineages of the postembryonic fly brain. Here, we review the role played by Imp and Syp gradients in several neural stem cell lineages, focusing on how they specify sequential neural fates through the post-transcriptional regulation of target genes, including the Chinmo and Mamo transcription factors. We further discuss how upstream inputs, including hormonal signals, modify the output of these gradients to couple neurogenesis with the development of the organism. Finally, we review the roles that the Imp and Syp gradients play beyond the generation of diversity, including the regulation of stem cell proliferation, the timing of neural stem cell lineage termination, and the coupling of neuronal birth order to circuit assembly.

Dissection of Drosophila Adult Brains for Patch-Clamping Neurons

The brain of adult flies (Drosophila melanogaster) has been studied in detail from several perspectives, including the anatomical and molecular characterization of hundreds of neuronal types. However, information regarding the electrophysiological properties of most neuronal types is lacking. This protocol provides detailed information on how to dissect the brain of adult flies to produce an ex vivo preparation in which central neurons can be patch-clamped. Immobilizing fresh and tiny tissues, such as fly brains, to perform successful patch-clamp recordings is a critical step; here, we explain how this can be achieved using cyanoacrylate glue.

(Digital Presentation) In Vivo Electrochemical Measurement of Dopamine in Adult Drosophila Mushroom Body

Dopamine is a neuromodulator that is secreted to the synapse to relay chemical signals to target neurons. Abnormal levels of dopamine release leads to various neurodegenerative diseases. Therefore, measuring dopamine is essential to understand how dopamine is regulated under normal and pathological conditions. Drosophila melanogaster, the fruit fly, is an ideal model system for studying fundamental neurological processes and diseases because of the availability of sophisticated genetic tools and well conserved neurological processes between mammals and flies. Majority of neuroscience studies involved in modifying a gene and measure the effect of genetic mutation on output behaviors. However, dopamine release is highly dynamic because of the complex activity of dopamine transporters and autoreceptors. Therefore, to understand how dopamine signaling controls the behavior, a direct measurement of changes in dopamine release is necessary. Fast-scan cyclic voltammetry (FSCV) at a carbon-fiber microelectrode is an electrochemical technique that trace concentration changes in dopamine release on the sub-second time scale. Our lab pioneered directly measuring various endogenous neuromodulators in the fly central nervous system with FSCV. Initially, these studies were performed in ex vivo preparations, where brains were isolated from larvae and adult fly, and thus could not monitor neuromodulators during behavior. In this study, we developed in vivo FSCV method to measure phasic dopamine in the mushroom body (MB) during behavior for the first time. The MB in fly has been extensively studied as an associative center for regulating olfactory learning and memory. First, acetylcholine stimulation was applied to the MB heel and medial tip to characterize dopamine signaling and to demonstrate the feasibility of in vivo FSCV in intact fly brain. Application of 0.2 pmol acetylcholine released 0.36 ± 0.06 µM dopamine in the medial tip, which is slightly higher than 0.22 ± 0.06 µM dopamine in the heel. Compartmental differences in evoked release suggest heterogeneity of dopamine regulation in the MB. Nisoxetine, a dopamine transporter inhibitor, and flupentixol, a D2 antagonist, increased stimulated dopamine release. We then applied the in vivo method to monitor changes in behaviorally evoked dopamine release during sugar feeding. Sugar feeding evoked 0.31 ± 0.09 µM dopamine in the medial tip of MB. Flupentixol significantly increased sugar evoked release implying D2 receptor acts as autoreceptor and regulates dopamine signaling during sugar feeding. Therefore, this developed in vivo FSCV method is a great addition to the existing tools to measure endogenous neuromodulators in the fly and valuable for studying real-time dopamine signaling during behavior. This in vivo method also can be further extended to better understand how dopamine and other neuromodulators regulate complex behaviors, such as reward associated learning and memory formation.

The neuronal logic of how internal states control food choice.

When deciding what to eat, animals evaluate sensory information about food quality alongside multiple ongoing internal states1-10. How internal states interact to alter sensorimotor processing and shape decisions such as food choice remains poorly understood. Here we use pan-neuronal volumetric activity imaging in the brain of Drosophila melanogaster to investigate the neuronal basis of internal state-dependent nutrient appetites. We created a functional atlas of the ventral fly brain and find that metabolic state shapes sensorimotor processing across large sections of the neuropil. By contrast, reproductive state acts locally to define how sensory information is translated into feeding motor output. These two states thus synergistically modulate protein-specific food intake and food choice. Finally, using a novel computational strategy, we identify driver lines that label neurons innervating state-modulated brain regions and show that the newly identified 'borboleta' region is sufficient to direct food choice towards protein-rich food. We thus identify a generalizable principle by which distinct internal states are integrated to shape decision making and propose a strategy to uncover and functionally validate how internal states shape behaviour.

A Programmable Ontology Encompassing the Functional Logic of the Drosophila Brain.

The Drosophila brain has only a fraction of the number of neurons of higher organisms such as mice and humans. Yet the sheer complexity of its neural circuits recently revealed by large connectomics datasets suggests that computationally modeling the function of fruit fly brain circuits at this scale poses significant challenges. To address these challenges, we present here a programmable ontology that expands the scope of the current Drosophila brain anatomy ontologies to encompass the functional logic of the fly brain. The programmable ontology provides a language not only for modeling circuit motifs but also for programmatically exploring their functional logic. To achieve this goal, we tightly integrated the programmable ontology with the workflow of the interactive FlyBrainLab computing platform. As part of the programmable ontology, we developed NeuroNLP++, a web application that supports free-form English queries for constructing functional brain circuits fully anchored on the available connectome/synaptome datasets, and the published worldwide literature. In addition, we present a methodology for including a model of the space of odorants into the programmable ontology, and for modeling olfactory sensory circuits of the antenna of the fruit fly brain that detect odorant sources. Furthermore, we describe a methodology for modeling the functional logic of the antennal lobe circuit consisting of a massive number of local feedback loops, a characteristic feature observed across Drosophila brain regions. Finally, using a circuit library, we demonstrate the power of our methodology for interactively exploring the functional logic of the massive number of feedback loops in the antennal lobe.

Genetic regulation of central synapse formation and organization in Drosophila melanogaster.

A goal of modern neuroscience involves understanding how connections in the brain form and function. Such a knowledge is essential to inform how defects in the exquisite complexity of nervous system growth influence neurological disease. Studies of the nervous system in the fruit fly Drosophila melanogaster enabled the discovery of a wealth of molecular and genetic mechanisms underlying development of synapses-the specialized cell-to-cell connections that comprise the essential substrate for information flow and processing in the nervous system. For years, the major driver of knowledge was the neuromuscular junction due to its ease of examination. Analogous studies in the central nervous system lagged due to a lack of genetic accessibility of specific neuron classes, synaptic labels compatible with cell-type-specific access, and high resolution, quantitative imaging strategies. However, understanding how central synapses form remains a prerequisite to understanding brain development. In the last decade, a host of new tools and techniques extended genetic studies of synapse organization into central circuits to enhance our understanding of synapse formation, organization, and maturation. In this review, we consider the current state-of-the-field. We first discuss the tools, technologies, and strategies developed to visualize and quantify synapses in vivo in genetically identifiable neurons of the Drosophila central nervous system. Second, we explore how these tools enabled a clearer understanding of synaptic development and organization in the fly brain and the underlying molecular mechanisms of synapse formation. These studies establish the fly as a powerful in vivo genetic model that offers novel insights into neural development.

Expression of a constitutively active insulin receptor in Drosulfakinin (Dsk) neurons regulates metabolism and sleep in Drosophila

The ability of organisms to sense their nutritional environment and adjust their behavior accordingly is critical for survival. Insulin-like peptides (ilps) play major roles in controlling behavior and metabolism; however, the tissues and cells that insulin acts on to regulate these processes are not fully understood. In the fruit fly, Drosophila melanogaster, insulin signaling has been shown to function in the fat body to regulate lipid storage, but whether ilps act on the fly brain to regulate nutrient storage is not known. In this study, we manipulate insulin signaling in defined populations of neurons in Drosophila and measure glycogen and triglyceride storage. Expressing a constitutively active form of the insulin receptor (dInR) in the insulin-producing cells had no effect on glycogen or triglyceride levels. However, activating insulin signaling in the Drosulfakinin (Dsk)-producing neurons led to triglyceride accumulation and increased food consumption. The expression of ilp2, ilp3 and ilp5 was increased in flies with activated insulin signaling in the Dsk neurons, which along with the feeding phenotype, may cause the triglyceride storage phenotypes observed in these flies. In addition, expressing a constitutively active dInR in Dsk neurons resulted in decreased sleep in the fed state and less starvation-induced sleep suppression suggesting a role for insulin signaling in regulating nutrient-responsive behaviors. Together, these data support a role for insulin signaling in the Dsk-producing neurons for regulating behavior and maintaining metabolic homeostasis.

From Photons to Behaviors: Neural Implementations of Visual Behaviors in Drosophila.

Neural implementations of visual behaviors in Drosophila have been dissected intensively in the past couple of decades. The availability of premiere genetic toolkits, behavioral assays in tethered or freely moving conditions, and advances in connectomics have permitted the understanding of the physiological and anatomical details of the nervous system underlying complex visual behaviors. In this review, we describe recent advances on how various features of a visual scene are detected by the Drosophila visual system and how the neural circuits process these signals and elicit an appropriate behavioral response. Special emphasis was laid on the neural circuits that detect visual features such as brightness, color, local motion, optic flow, and translating or approaching visual objects, which would be important for behaviors such as phototaxis, optomotor response, attraction (or aversion) to moving objects, navigation, and visual learning. This review offers an integrative framework for how the fly brain detects visual features and orchestrates an appropriate behavioral response.

Hormone-controlled changes in the differentiation state of post-mitotic neurons

While we think of neurons as having a fixed identity, many show spectacular plasticity.1-10 Metamorphosis drives massive changes in the fly brain;11,12 neurons that persist into adulthood often change in response to the steroid hormone ecdysone.13,14 Besides driving remodeling,11-14 ecdysone signaling can also alter the differentiation status of neurons.7,15 The three sequentially born subtypes of mushroom body (MB) Kenyon cells (γ, followed by α'/β', and finally α/β)16 serve as a model of temporal fating.17-21 γ neurons are also used as a model of remodeling during metamorphosis. As γ neurons are the only functional Kenyon cells in the larval brain, they serve the function of all three adult subtypes. Correspondingly, larval γ neurons have a similar morphology to α'/β' and α/β neurons-their axons project dorsally and medially. During metamorphosis, γ neurons remodel to form a single medial projection. Both temporal fate changes and defects in remodeling therefore alter γ-neuron morphology in similar ways. Mamo, a broad-complex, tramtrack, and bric-à-brac/poxvirus and zinc finger (BTB/POZ)transcription factor critical for temporal specification of α'/β' neurons,18,19 was recently described as essential for γ remodeling.22 In a previous study, we noticed a change in the number of adult Kenyon cells expressing γ-specific markers when mamo was manipulated.18 These data implied a role for Mamo in γ-neuron fate specification, yet mamo is not expressed in γ neurons until pupariation,18,22 well past γ specification. This indicates that mamo has a later role in ensuring that γ neurons express the correct Kenyon cell subtype-specific genes in the adult brain.

Emergence of Integrated Information at Macro Timescales in Real Neural Recordings.

How a system generates conscious experience remains an elusive question. One approach towards answering this is to consider the information available in the system from the perspective of the system itself. Integrated information theory (IIT) proposes a measure to capture this integrated information (Φ). While Φ can be computed at any spatiotemporal scale, IIT posits that it be applied at the scale at which the measure is maximised. Importantly, Φ in conscious systems should emerge to be maximal not at the smallest spatiotemporal scale, but at some macro scale where system elements or timesteps are grouped into larger elements or timesteps. Emergence in this sense has been demonstrated in simple example systems composed of logic gates, but it remains unclear whether it occurs in real neural recordings which are generally continuous and noisy. Here we first utilise a computational model to confirm that Φ becomes maximal at the temporal scales underlying its generative mechanisms. Second, we search for emergence in local field potentials from the fly brain recorded during wakefulness and anaesthesia, finding that normalised Φ (wake/anaesthesia), but not raw Φ values, peaks at 5 ms. Lastly, we extend our model to investigate why raw Φ values themselves did not peak. This work extends the application of Φ to simple artificial systems consisting of logic gates towards searching for emergence of a macro spatiotemporal scale in real neural systems.

Tau-Induced Elevation of the Activity-Regulated Cytoskeleton Associated Protein Arc1 Causally Mediates Neurodegeneration in the Adult Drosophila Brain

Alzheimer’s disease and other tauopathies are neurodegenerative disorders pathologically defined by aggregated forms of tau protein in the brain. While synaptic degradation is a well-established feature of tau-induced neurotoxicity, the underlying mechanisms of how pathogenic forms of tau drive synaptic dysfunction are incompletely understood. Synaptic function and subsequent memory consolidation are dependent upon synaptic plasticity, the ability of synapses to adjust their structure and strength in response to changes in activity. The activity regulated cytoskeleton associated protein ARC acts in the nucleus and at postsynaptic densities to regulate various forms of synaptic plasticity. ARC harbors a retrovirus-like Gag domain that facilitates ARC multimerization and capsid formation. Trans-synaptic transfer of RNA-containing ARC capsids is required for synaptic plasticity. While ARC is elevated in brains of patients with Alzheimer’s disease and genetic variants in ARC increase susceptibility to Alzheimer’s disease, mechanistic insight into the role of ARC in Alzheimer’s disease is lacking. Using a Drosophila model of tauopathy, we find that pathogenic tau significantly increases multimeric species of the protein encoded by the Drosophila homolog of ARC, Arc1, in the adult fly brain. We find that Arc1 is elevated within nuclei and the neuropil of tau transgenic Drosophila, but does not localize to synaptic vesicles or presynaptic terminals. Lastly, we find that genetic manipulation of Arc1 modifies tau-induced neurotoxicity, suggesting that tau-induced Arc1 elevation mediates neurodegeneration. Taken together, our results suggest that ARC elevation in human Alzheimer’s disease is a consequence of tau pathology and is a causal factor contributing to neuronal death.

Pairing-Dependent Plasticity in a Dissected Fly Brain Is Input-Specific and Requires Synaptic CaMKII Enrichment and Nighttime Sleep.

In Drosophila, in vivo functional imaging studies revealed that associative memory formation is coupled to a cascade of neural plasticity events in distinct compartments of the mushroom body (MB). In-depth investigation of the circuit dynamics, however, will require an ex vivo model that faithfully mirrors these events to allow direct manipulations of circuit elements that are inaccessible in the intact fly. The current ex vivo models have been able to reproduce the fundamental plasticity of aversive short-term memory, a potentiation of the MB intrinsic neuron (Kenyon cells [KCs]) responses after artificial learning ex vivo. However, this potentiation showed different localization and encoding properties from those reported in vivo and failed to generate the previously reported suppression plasticity in the MB output neurons (MBONs). Here, we develop an ex vivo model using the female Drosophila brain that recapitulates behaviorally evoked plasticity in the KCs and MBONs. We demonstrate that this plasticity accurately localizes to the MB α′3 compartment and is encoded by a coincidence between KC activation and dopaminergic input. The formed plasticity is input-specific, requiring pairing of the conditioned stimulus and unconditioned stimulus pathways; hence, we name it pairing-dependent plasticity. Pairing-dependent plasticity formation requires an intact CaMKII gene and is blocked by previous-night sleep deprivation but is rescued by rebound sleep. In conclusion, we show that our ex vivo preparation recapitulates behavioral and imaging results from intact animals and can provide new insights into mechanisms of memory formation at the level of molecules, circuits, and brain state.SIGNIFICANCE STATEMENT The mammalian ex vivo LTP model enabled in-depth investigation of the hippocampal memory circuit. We develop a parallel model to study the Drosophila mushroom body (MB) memory circuit. Pairing activation of the conditioned stimulus and unconditioned stimulus pathways in dissected brains induces a potentiation pairing-dependent plasticity (PDP) in the axons of α′β′ Kenyon cells and a suppression PDP in the dendrites of their postsynaptic MB output neurons, localized in the MB α′3 compartment. This PDP is input-specific and requires the 3′ untranslated region of CaMKII. Interestingly, ex vivo PDP carries information about the animal's experience before dissection; brains from sleep-deprived animals fail to form PDP, whereas those from animals who recovered 2 h of their lost sleep form PDP.

The Neuromodulatory Basis of Aggression: Lessons From the Humble Fruit Fly.

Aggression is an intrinsic trait that organisms of almost all species, humans included, use to get access to food, shelter, and mating partners. To maximize fitness in the wild, an organism must vary the intensity of aggression toward the same or different stimuli. How much of this variation is genetic and how much is externally induced, is largely unknown but is likely to be a combination of both. Irrespective of the source, one of the principal physiological mechanisms altering the aggression intensity involves neuromodulation. Any change or variation in aggression intensity is most likely governed by a complex interaction of several neuromodulators acting via a meshwork of neural circuits. Resolving aggression-specific neural circuits in a mammalian model has proven challenging due to the highly complex nature of the mammalian brain. In that regard, the fruit fly model Drosophila melanogaster has provided insights into the circuit-driven mechanisms of aggression regulation and its underlying neuromodulatory basis. Despite morphological dissimilarities, the fly brain shares striking similarities with the mammalian brain in genes, neuromodulatory systems, and circuit-organization, making the findings from the fly model extremely valuable for understanding the fundamental circuit logic of human aggression. This review discusses our current understanding of how neuromodulators regulate aggression based on findings from the fruit fly model. We specifically focus on the roles of Serotonin (5-HT), Dopamine (DA), Octopamine (OA), Acetylcholine (ACTH), Sex Peptides (SP), Tachykinin (TK), Neuropeptide F (NPF), and Drosulfakinin (Dsk) in fruit fly male and female aggression.

The Role of microRNAs in the Drosophila Melanogaster Visual System.

MicroRNAs (miRNAs) are a class of small non-coding RNAs (∼22 nucleotides in length) that negatively regulate protein-coding gene expression post-transcriptionally by targeting mRNAs and triggering either translational repression or RNA degradation. MiRNA genes represent approximately 1% of the genome of different species and it has been estimated that every miRNA can interact with an average of 200 mRNA transcripts, with peaks of 1,500 mRNA targets per miRNA molecule. As a result, miRNAs potentially play a fundamental role in several biological processes including development, metabolism, proliferation, and apoptotic cell death, both in physiological and pathological conditions. Since miRNAs were discovered, Drosophila melanogaster has been used as a model organism to shed light on their functions and their molecular mechanisms in the regulation of many biological and behavioral processes. In this review we focus on the roles of miRNAs in the fruit fly brain, at the level of the visual system that is composed by the compound eyes, each containing ∼800 independent unit eyes called ommatidia, and each ommatidium is composed of eight photoreceptor neurons that project into the optic lobes. We describe the roles of a set of miRNAs in the development and in the proper function of the optic lobes (bantam, miR-7, miR-8, miR-210) and of the compound eyes (bantam, miR-7, miR-9a, miR-210, miR-263a/b, miR-279/996), summarizing also the pleiotropic effects that some miRNAs exert on circadian behavior.