Pharmacological evidence for GABAergic regulation of specific behaviors in Drosophila melanogaster.

We have identified several GABAergic-modulated behaviors in Drosophila melanogaster by employing a pharmacological approach to disrupt GABA transporter function in vivo. Systemic treatment of adult female flies with the GABA transport inhibitors DL-2,4-diaminobutyric acid (DABA) or R,S-nipecotic acid (NipA), resulted in diminished locomotor activity, deficits in geotaxis, and the induction of convulsive behaviors with a secondary loss of the righting reflex. Pharmacological evidence suggested that the observed behavioral phenotypes were specific to disruption of GABA transporter function and GABAergic activity. The effects of GABA reuptake inhibitors on locomotor activity were dose dependent, pharmacologically distinct, and paralleled their known effects in mammalian systems. Recovery of normal locomotor activity and the righting reflex in DABA- and NipA-treated flies was achieved by coadministration of bicuculline (BIC), a GABA receptor antagonist that supresses GABAergic activity in mammals. Recovery of these behaviors was also achieved by coadministration of gabapentin, an anticonvulsant agent that interacts with mammalian GABAergic systems. Finally, behavioral effects were selective because other specific behaviors such as feeding activity and female sexual receptivity were not affected. Related pharmacological analyses performed in vitro on isolated Drosophila synaptic plasma membrane vesicles demonstrated high affinity, saturable uptake mechanisms for [3H]-GABA; further competitive inhibition studies with DABA and NipA demonstrated their ability to inhibit [3H]-GABA transport. The existence of experimentally accessible GABA transporters in Drosophila that share conserved pharmacological properties with their mammalian counterparts has resulted in the identification of specific behaviors that are modulated by GABA.     

Courtship, aggression and avoidance: pheromones, receptors and neurons for social behaviors in Drosophila

Chemical communication between individual Drosophila is extremely important for social behaviors required for survival and reproduction, such as con-specific recognition, courtship, aggression and avoidance of odor from "stressed" flies. Characterization of the receptors and neural circuits that detect pheromone cues and an understanding of how these circuits are modulated by the social interactions are fundamental questions about the neurobiology of social behaviors. Recent years have seen important advances in the identification of chemoreceptors and sensory neurons that are involved in sensing pheromones. Here we present a brief review of the current understanding of the peripheral chemosensory systems that are involved in social behaviors.     

The origin of behavioral bursts in decision-making circuitry

From ants to humans, the timing of many animal behaviors comes in bursts of activity separated by long periods of inactivity. Recently, mathematical modeling has shown that simple algorithms of priority-driven behavioral choice can result in bursty behavior. To experimentally test this link between decision-making circuitry and bursty dynamics, we have turned to Drosophila melanogaster. We have found that the statistics of intervals between activity periods in endogenous activity-rest switches of wild-type Drosophila are very well described by the Weibull distribution, a common distribution of bursty dynamics in complex systems. The bursty dynamics of wild-type Drosophila walking activity are shown to be determined by this inter-event distribution alone and not by memory effects, thus resembling human dynamics. Further, using mutant flies that disrupt dopaminergic signaling or the mushroom body, circuitry implicated in decision-making, we show that the degree of behavioral burstiness can be modified. These results are thus consistent with the proposed link between decision-making circuitry and bursty dynamics, and highlight the importance of using simple experimental systems to test general theoretical models of behavior. The findings further suggest that analysis of bursts could prove useful for the study and evaluation of decision-making circuitry.     

Drosophila with postponed aging as a model for aging research.

Species of the genus Drosophila, commonly known as "fruitflies," are good model systems for research in aging. Drosophila are extremely well-known genetically, developmentally, and otherwise. They are also genetically analogous to mammalian species in most important respects. Previous work with Drosophila has been hampered by inbreeding depression, but more recent work using selection has created Drosophila with postponed aging that is inherited normally. Genetic transformation has also increased Drosophila life spans in some cases. Several biologic approaches have been applied to the analysis of genetically postponed aging in Drosophila: quantitative genetics, organismal physiology, and protein electrophoresis. Ultimately, these different approaches will be integrated into an overall analysis of aging in Drosophila, one that could be valuable for research with other taxa as well.     

Competition and compensation: coupled to death in development and cancer

Developing systems exhibit robust and tolerant properties in the form of compensation and competition within cell groups. Fundamentally, these behaviors are governed by mechanisms that elicit proliferation and apoptosis. Recent insights from the Drosophila system implicate new determinants that specify "winners" and "losers" in this process.     

Cellular bases of behavioral plasticity: establishing and modifying synaptic circuits in the Drosophila genetic system

Genetic malleability and amenability to behavioral assays make Drosophila an attractive model for dissecting the molecular mechanisms of complex behaviors, such as learning and memory. At a cellular level, Drosophila has contributed a wealth of information on the mechanisms regulating membrane excitability and synapse formation, function, and plasticity. Until recently, however, these studies have relied almost exclusively on analyses of the peripheral neuromuscular junction, with a smaller body of work on neurons grown in primary culture. These experimental systems are, by themselves, clearly inadequate for assessing neuronal function at the many levels necessary for an understanding of behavioral regulation. The pressing need is for access to physiologically relevant neuronal circuits as they develop and are modified throughout life. In the past few years, progress has been made in developing experimental approaches to examine functional properties of identified populations of Drosophila central neurons, both in cell culture and in vivo. This review focuses on these exciting developments, which promise to rapidly expand the frontiers of functional cellular neurobiology studies in Drosophila. We discuss here the technical advances that have begun to reveal the excitability and synaptic transmission properties of central neurons in flies, and discuss how these studies promise to substantially increase our understanding of neuronal mechanisms underlying behavioral plasticity.     

Aggression and courtship in Drosophila: pheromonal communication and sex recognition

Upon encountering a conspecific in the wild, males have to rapidly detect, integrate and process the most relevant signals to evoke an appropriate behavioral response. Courtship and aggression are the most important social behaviors in nature for procreation and survival: for males, making the right choice between the two depends on the ability to identify the sex of the other individual. In flies as in most species, males court females and attack other males. Although many sensory modalities are involved in sex recognition, chemosensory communication mediated by specific molecules that serve as pheromones plays a key role in helping males distinguish between courtship and aggression targets. The chemosensory signals used by flies include volatile and non-volatile compounds, detected by the olfactory and gustatory systems. Recently, several putative olfactory and gustatory receptors have been identified that play key roles in sex recognition, allowing investigators to begin to map the neuronal circuits that convey this sensory information to higher processing centers in the brain. Here, we describe how Drosophila melanogaster males use taste and smell to make correct behavioral choices.     

Research progress on Drosophila visual cognition in China

Visual cognition,as one of the fundamental aspects of cognitive neuroscience,is generally associated with high-order brain functions in animals and human.Drosophila,as a model organism,shares certain features of visual cognition in common with mammals at the genetic,molecular,cellular,and even higher behavioral levels.From learning and memory to decision making,Drosophila covers a broad spectrum of higher cognitive behaviors beyond what we had expected.Armed with powerful tools of genetic manipulation in Drosophila,an increasing number of studies have been conducted in order to elucidate the neural circuit mechanisms underlying these cognitive behaviors from a genes-brain-behavior perspective.The goal of this review is to integrate the most important studies on visual cognition in Drosophila carried out in mainland China during the last decade into a body of knowledge encompassing both the basic neural operations and circuitry of higher brain function in Drosophila.Here,we consider a series of the higher cognitive behaviors beyond learning and memory,such as visual pattern recognition,feature and context generalization,different feature memory traces,salience-based decision,attention-like behavior,and cross-modal leaning and memory.We discuss the possible general gain-gating mechanism implementing by dopamine-mushroom body circuit in fly's visual cognition.We hope that our brief review on this aspect will inspire further study on visual cognition in flies,or even beyond.     

Contrasting mechanisms of stem cell maintenance in Drosophila

Stem cells are self-renewing multipotent cells essential for development or homeostasis of many tissues. Stem cell populations can be found in most multicellular plants and animals. The mechanisms by which these populations are maintained are diverse, utilizing both intrinsic and extrinsic factors to regulate cell division and differentiation. The genetic tools of the fruitfly, Drosophila melanogaster, have permitted detailed characterization of two stem cell populations. In this review, we will examine these contrasting stem cell model systems from Drosophila and their relevance to stem cell populations in other organisms.     

Neuropeptides and their precursors in the fruitfly, Drosophila melanogaster

Neuropeptides form the most diverse class of chemical messenger molecules in metazoan nervous systems. They are usually generated from biosynthetic precursor polypeptides by enzymatic processing and modification. Many different peptides belonging to a number of distinct neuropeptide families have already been characterized from various insect species. The Drosophila Genome Sequencing Project has important implications for the future of neurobiological research. This paper describes the discovery of several new fruitfly neuropeptides by an in silico data mining approach. In addition, the state-of-the-art of Drosophila peptide research is reviewed.     

Breaking cellular symmetry along planar axes in Drosophila and vertebrates

In many organs, epithelial cells are polarized not only along the apicobasal axis, but also along a second axis within a plane. Acquisition of the latter polarity, known as planar cell polarity (PCP) or tissue polarity, is crucial for specialized cellular functions. Genetic programming of PCP has been most thoroughly studied in Drosophila, which has allowed identification of a number of regulatory molecules that are evolutionally conserved. One group of the regulators is responsible for interpreting a hypothetical polarity cue and directing local cytoskeletal reorganization. This group includes a seven-pass transmembrane cadherin known as Flamingo (also known as Starry night), other receptors, and downstream components; and many of those molecules are redistributed to restricted subcellular compartments. Recent studies on a trio of cell-surface molecules challenge a previous hypothesis about the identity of the polarity cue and prompt a novel hypothesis about a global input. Studies on vertebrate systems support the notion that the molecular mechanisms demonstrated in Drosophila are applicable to at least two classes of polarized behaviors of vertebrate cells: sensory hair morphogenesis in the inner ear epithelium, and convergent extension movements during gastrulation.     

离子通道蛋白在果蝇大脑神经上皮干细胞发育中的功能研究

离子通道蛋白作为神经系统的重要组成部分,在早期神经细胞发育中的作用却没有被研究过。基于神经发育在果蝇与小鼠间的保守性,果蝇幼虫大脑视觉中心可作为很好的模型来筛选参与神经干细胞行为调节的基因。文章通过体内RNA干扰和失活突变体来研究重要的钙离子通道和钾离子通道蛋白对神经干细胞的调节作用。结果表明,这些蛋白表达水平降低和shaker蛋白完全失活均对果蝇幼虫大脑神经干细胞的发育无影响。     

Power tools for gene expression and clonal analysis in Drosophila

The development of two-component expression systems in Drosophila melanogaster, one of the most powerful genetic models, has allowed the precise manipulation of gene function in specific cell populations. These expression systems, in combination with site-specific recombination approaches, have also led to the development of new methods for clonal lineage analysis. We present a hands-on user guide to the techniques and approaches that have greatly increased resolution of genetic analysis in the fly, with a special focus on their application for lineage analysis. Our intention is to provide guidance and suggestions regarding which genetic tools are most suitable for addressing different developmental questions.     

The pheromonal role of cuticular hydrocarbons in Drosophila melanogaster

Pheromones play a curcial role in mate stimulation and discrimination. In the fruit fly Drosophila, the most abundant cuticular hydrocarbons act as sex pheromones during courtship behavior. There are several active molecules and they compose a sex- and species-specific pheromonal bouquet. Different species from the Drosophila melanogaster subgroup have adopted alternative systems of chemical mate recognition. Recent exploration of these interspecific variations, and of intraspecific variations, has led to the characterization of genes and to the mapping of structures that process the production and perception of chemical messages.     

Fruit fly behavior in response to chemosensory signals

An important question in contemporary sensory neuroscience is how animals perceive their environment and make appropriate behavioral choices based on chemical perceptions. The fruit fly Drosophila melanogaster exhibits robust tastant and odor-evoked behaviors. Understanding how the gustatory and olfactory systems support the perception of these contact and volatile chemicals and translate them into appropriate attraction or avoidance behaviors has made an unprecedented contribution to our knowledge of the organization of chemosensory systems. In this review, I begin by describing the receptors and signaling mechanisms of the Drosophila gustatory and olfactory systems and then highlight their involvement in the control of simple and complex behaviors. The topics addressed include feeding behavior, learning and memory, navigation behavior, neuropeptide modulation of chemosensory behavior, and I conclude with a discussion of recent work that provides insight into pheromone signaling pathways.     

The neurobiology of sensing respiratory gases for the control of animal behavior

Aerobic metabolism is fundamental for almost all animal life.Cellular consumption of oxygen (O2) and production of carbon dioxide (CO2) signal metabolic states and physiologic stresses.These respirator...     

果蝇干细胞研究进展

本文主要介绍了果蝇五种干细胞,包括生殖干细胞、神经干细胞、造血干细胞、小肠干细胞、肾干细胞及其微环境（niche）的组成成份;简述了五种干细胞系统对应的分子标记;最后重点介绍了调控每种干细胞系统的信号通路。     

Fungal mating pheromones: choreographing the dating game

Pheromones are ubiquitous from bacteria to mammals - a testament to their importance in regulating inter-cellular communication. In fungal species, they play a critical role in choreographing interactions between mating partners during the program of sexual reproduction. Here, we describe how fungal pheromones are synthesized, their interactions with G protein-coupled receptors, and the signals propagated by this interaction, using Saccharomyces cerevisiae as a reference point. Divergence from this model system is compared amongst the ascomycetes and basidiomycetes, which reveals the wealth of information that has been gleaned from studying pheromone-driven processes across a wide spectrum of the fungal kingdom.     

Studying aggression in Drosophila (fruit flies)

Aggression is an innate behavior that evolved in the framework of defending or obtaining resources. This complex social behavior is influenced by genetic, hormonal and environmental factors. In many organisms, aggression is critical to survival but controlling and suppressing aggression in distinct contexts also has become increasingly important. In recent years, invertebrates have become increasingly useful as model systems for investigating the genetic and systems biological basis of complex social behavior. This is in part due to the diverse repertoire of behaviors exhibited by these organisms. In the accompanying video, we outline a method for analyzing aggression in Drosophila whose design encompasses important eco-ethological constraints. Details include steps for: making a fighting chamber; isolating and painting flies; adding flies to the fight chamber; and video taping fights. This approach is currently being used to identify candidate genes important in aggression and in elaborating the neuronal circuitry that underlies the output of aggression and other social behaviors.