Fruit Fly Brain Research Articles

Memory Elicited by Courtship Conditioning Requires Mushroom Body Neuronal Subsets Similar to Those Utilized in Appetitive Memory.

An animal’s ability to learn and to form memories is essential for its survival. The fruit fly has proven to be a valuable model system for studies of learning and memory. One learned behavior in fruit flies is courtship conditioning. In Drosophila courtship conditioning, male flies learn not to court females during training with an unreceptive female. He retains a memory of this training and for several hours decreases courtship when subsequently paired with any female. Courtship conditioning is a unique learning paradigm; it uses a positive-valence stimulus, a female fly, to teach a male to decrease an innate behavior, courtship of the female. As such, courtship conditioning is not clearly categorized as either appetitive or aversive conditioning. The mushroom body (MB) region in the fruit fly brain is important for several types of memory; however, the precise subsets of intrinsic and extrinsic MB neurons necessary for courtship conditioning are unknown. Here, we disrupted synaptic signaling by driving a shibirets effector in precise subsets of MB neurons, defined by a collection of split-GAL4 drivers. Out of 75 lines tested, 32 showed defects in courtship conditioning memory. Surprisingly, we did not have any hits in the γ lobe Kenyon cells, a region previously implicated in courtship conditioning memory. We did find that several γ lobe extrinsic neurons were necessary for courtship conditioning memory. Overall, our memory hits in the dopaminergic neurons (DANs) and the mushroom body output neurons were more consistent with results from appetitive memory assays than aversive memory assays. For example, protocerebral anterior medial DANs were necessary for courtship memory, similar to appetitive memory, while protocerebral posterior lateral 1 (PPL1) DANs, important for aversive memory, were not needed. Overall, our results indicate that the MB circuits necessary for courtship conditioning memory coincide with circuits necessary for appetitive memory.

The I in Scientist

The I in Scientist

Local Versus Global Effects of Isoflurane Anesthesia on Visual Processing in the Fly Brain.

What characteristics of neural activity distinguish the awake and anesthetized brain? Drugs such as isoflurane abolish behavioral responsiveness in all animals, implying evolutionarily conserved mechanisms. However, it is unclear whether this conservation is reflected at the level of neural activity. Studies in humans have shown that anesthesia is characterized by spatially distinct spectral and coherence signatures that have also been implicated in the global impairment of cortical communication. We questioned whether anesthesia has similar effects on global and local neural processing in one of the smallest brains, that of the fruit fly (Drosophila melanogaster). Using a recently developed multielectrode technique, we recorded local field potentials from different areas of the fly brain simultaneously, while manipulating the concentration of isoflurane. Flickering visual stimuli (‘frequency tags’) allowed us to track evoked responses in the frequency domain and measure the effects of isoflurane throughout the brain. We found that isoflurane reduced power and coherence at the tagging frequency (13 or 17 Hz) in central brain regions. Unexpectedly, isoflurane increased power and coherence at twice the tag frequency (26 or 34 Hz) in the optic lobes of the fly, but only for specific stimulus configurations. By modeling the periodic responses, we show that the increase in power in peripheral areas can be attributed to local neuroanatomy. We further show that the effects on coherence can be explained by impacted signal-to-noise ratios. Together, our results show that general anesthesia has distinct local and global effects on neuronal processing in the fruit fly brain.

Mass spectrometry imaging of lipids and metabolites: from fruit fly brains to single nanometer vesicles

Alzheimer׳s disease is one of the main causes of dementia in the elderly and its frequency is on the rise worldwide. It is considered the result of complex interactions between genetic and environmental factors, being many of them unknown. Therefore, there is a dire necessity for the identification of novel molecular players for the understanding of this disease. In this data article we determined the protein expression profiles of whole protein extracts from cortex regions of brains from patients with Alzheimer׳s disease in comparison to a normal brain. We identified 721 iTRAQ-labeled polypeptides with more than 95% in confidence. We analyzed all proteins that changed in their expression level and located them in the KEGG metabolic pathways, as well as in the mitochondrial complexes of the electron transport chain and ATP synthase. In addition, we analyzed the over- and sub-expressed polypeptides through IPA software, specifically Core I and Biomarkers I modules. Data in this article is related to the research article “Identification of proteins that are differentially expressed in brains with Alzheimer’s disease using iTRAQ labeling and tandem mass spectrometry” (Minjarez et al., 2016) [1].

Finalists selected for prize to turn data into science products

Projects that would make air quality, clinical trial, and emerging disease data more readily available are among the finalists for the Open Science Prize. The competition is designed to take the vast trove of government and other open data and turn it into products that can be used by scientists and the public. The six finalists use data generated in air-quality monitoring, clinical trials, pathogen surveillance, brain imaging, fruit fly brain research, and genetics investigations. They were chosen from among 96 international teams that submitted ideas. Each finalist team will receive $80,000 to turn its idea into a prototype by this December. The winner will be announced in February or March 2017. “We’re supporting these six international teams of innovators so that they can demonstrate the exciting potential of open science both to advance discovery and, through the application of research, to improve health across the world,” says Clare Matterson,

Synchronous Drosophila circadian pacemakers display nonsynchronous Ca²⁺ rhythms in vivo.

In Drosophila, molecular clocks control circadian rhythmic behavior through a network of ~150 pacemaker neurons. To explain how the network's neuronal properties encode time, we performed brainwide calcium imaging of groups of pacemaker neurons in vivo for 24 hours. Pacemakers exhibited daily rhythmic changes in intracellular Ca(2+) that were entrained by environmental cues and timed by molecular clocks. However, these rhythms were not synchronous, as each group exhibited its own phase of activation. Ca(2+) rhythms displayed by pacemaker groups that were associated with the morning or evening locomotor activities occurred ~4 hours before their respective behaviors. Loss of the receptor for the neuropeptide PDF promoted synchrony of Ca(2+) waves. Thus, neuropeptide modulation is required to sequentially time outputs from a network of synchronous molecular pacemakers.

Layered versatility atop circadian clocks

Circadian Rhythms The circadian clock evolved to allow cells or organisms to anticipate changes in physiological requirements associated with Earth's 24-hour light/dark cycle. Some activities, however, need to occur out of phase with the core clock. Liang et al. imaged changes in intracellular concentration of Ca2+ in populations of neurons in the fruit fly brain. Although the underlying clock was synchronous, the rhythms of Ca2+ changes corresponded with distinct timing of activities associated with activity of the particular neuronal populations. Proper coordination of these distinct phases required expression of the neuropeptide pigment-dispersing factor and its receptor. Science , this issue p. [976][1] [1]: /lookup/doi/10.1126/science.aad3997

Visualization and Quantification for Interactive Analysis of Neural Connectivity inDrosophila

Neurobiologists investigate the brain of the common fruit fly Drosophila melanogaster to discover neural circuits and link them to complex behaviour. Formulating new hypotheses about connectivity requires potential connectivity information between individual neurons, indicated by overlaps of arborizations of two or more neurons. As the number of higher order overlaps i.e. overlaps of three or more arborizations increases exponentially with the number of neurons under investigation, visualization is impeded by clutter and quantification becomes a burden. Existing solutions are restricted to visual or quantitative analysis of pairwise overlaps, as they rely on precomputed overlap data. We present a novel tool that complements existing methods for potential connectivity exploration by providing for the first time the possibility to compute and visualize higher order arborization overlaps on the fly and to interactively explore this information in both its spatial anatomical context and on a quantitative level. Qualitative evaluation by neuroscientists and non-experts demonstrated the utility and usability of the tool.

Mini review: Multielectrode recordings in insect brains

Currently, more and more laboratories are acquiring the capability of simultaneously detecting the extracellular activity of neuronal populations in anaesthetized and awake animals by multielectrode recordings. In insects, multielectrode recordings are challenging due to the small size of the nervous system. Nevertheless, multielectrode recordings have been successfully established in brains of cockroaches, honeybees, fruit flies and grasshoppers to study sensory processing related to mechanosensation, olfaction, vision and audition. The number of neurons which can be recorded using such multielectrode did not exceed 5 and likely depends on factors like recorded compartment of the neuron, impedance of the multielectrode, number of wires included in the multielectrode and threshold for spike detection. Signal-to-noise ratio (SNR) of the recordings obviously depends on the material and method used for production of multielectrodes. To mark the location of the recording, different methods like current-driven copper deposition, labelling with fluorescent dye and electrocoagulation of nervous tissue are used. As expected, multielectrode recordings are more difficult in freely moving compared to restricted insects due to movement artifacts and requirement for fixed placement of the multielectrode at a particular recording site in the CNS. Specific differences among different preparations and sensory systems like disentangling spike collisions in auditory stimulation increase in SNR after some time in olfactory systems and photoelectrical effect from compound eye in visual stimulation may require special attention and particular adaptations.

The Matrix Proteins Hasp and Hig Exhibit Segregated Distribution within Synaptic Clefts and Play Distinct Roles in Synaptogenesis

The synaptic cleft is the space through which neurotransmitters convey neural information between two synaptic terminals. This space is presumably filled with extracellular matrix molecules involved in synaptic function or differentiation. However, little is known about the identities of the matrix components, and it remains unclear how these molecules organize the matrix in synaptic clefts. In this study, we identified Hasp, a Drosophila secretory protein containing CCP and WAP domains. Molecular genetic analysis revealed that Hasp diffuses extracellularly and is predominantly captured at synaptic clefts of cholinergic synapses. Furthermore, Hasp regulates levels of DLG and the nAChR subunits Dα6 and Dα7 at postsynaptic terminals. Hasp is required for trapping of another matrix protein, Hig, which is also secreted and diffused in the brain, at synaptic clefts of cholinergic synapses; however, Hig is dispensable for localization of Hasp at synaptic clefts. In addition, in the brains of triple mutants for the nAChR subunits Dα5, Dα6, and Dα7, the level of Hig, but not Hasp, was markedly reduced in synaptic regions, indicating that these nAChR subunits are required to anchor Hig to synaptic clefts. High-resolution microscopy revealed that Hasp and Hig exhibit segregated distribution within individual synaptic clefts, reflecting their differing roles in synaptogenesis. These data provide insight into how Hasp and Hig construct the synaptic cleft matrix and regulate the differentiation of cholinergic synapses, and also illuminate a previously unidentified architecture within synaptic clefts. The synapse has been extensively studied because it is essential for neurotransmission. By contrast, the space between the synaptic terminals, the synaptic cleft, is still an undeveloped research area despite its ubiquity in synapses. In fruit fly brains, we obtained evidence that the matrix protein Hasp and the previously identified Hig, both of which are secreted extracellularly, localize predominantly to synaptic clefts of cholinergic synapses, and modulate the levels of nAChR subunits on postsynaptic membranes. However, Hasp and Hig play differential roles in matrix formation and exhibit segregated distribution within synaptic clefts. These results reveal the molecular mechanisms of synaptic matrix construction and illuminate a molecular architecture within synaptic clefts previously unrevealed in any animal species.

From GUI to GPU: A toolchain for GPU code generation for large scale Drosophila simulations using SpineML

From GUI to GPU: A toolchain for GPU code generation for large scale Drosophila simulations using SpineML

Closed-Loop Behavioral Control Increases Coherence in the Fly Brain.

We show that closed-loop control of a visual stimulus promotes temporal coordination across the Drosophila brain, compared with open-loop replay of the same visual sequences. This is significant because it suggests that, to understand goal-directed behavior or visual attention in flies, it may be most informative to sample neural activity from multiple regions across the brain simultaneously, and to examine temporal relationships (e.g., coherence) between these regions.

Neuroscience: hot on the trail of temperature processing.

Two studies investigate how information about temperature is processed in the brains of fruit flies, and reveal that different neuronal pathways transmit heating and cooling signals to higher brain regions. See Letters p.353 & p.358 Animals detect changes in external temperatures via thermoreceptors in the peripheral nervous system, but the central circuits that then process such signals have been unknown. Now two studies, led by Rachel Wilson and Marco Gallio, report distinct classes of neurons in the fly brain, which respond to external cooling, warming, or both, and contribute to behavioural response. The results illustrate how higher brain centres extract the quality, intensity and timing of a stimulus from a simple temperature map at the periphery.

A big picture of a small brain.

A detailed map of the neurons that carry information away from the mushroom bodies in the brains of fruit flies has improved our understanding of the ways in which experiences can modify behaviour.

Modulation of innate and learned sexual behaviors by the TRP channel Painless expressed in the fruit fly brain: behavioral genetic analysis and its implications.

Transient receptor potential (TRP) channels have attracted considerable attention because of their vital roles in primary sensory neurons, mediating responses to a wide variety of external environmental stimuli. However, much less is known about how TRP channels in the brain respond to intrinsic signals and are involved in neurophysiological processes that control complex behaviors. Painless (Pain) is the Drosophila TRP channel that was initially identified as a molecular sensor responsible for detecting noxious thermal and mechanical stimuli. Here, we review recent behavioral genetic studies demonstrating that Pain expressed in the brain plays a critical role in both innate and learned aspects of sexual behaviors. Several members of the TRP channel superfamily play evolutionarily conserved roles in sensory neurons as well as in other peripheral tissues. It is thus expected that brain TRP channels in vertebrates and invertebrates would have some common physiological functions. Studies of Pain in the Drosophila brain using a unique combination of genetics and physiological techniques should provide valuable insights into the fundamental principles concerning TRP channels expressed in the vertebrate and invertebrate brains.

Maintaining neural stem cell identity in the brain.

In the developing fruit fly brain, a protein called Trithorax increases the number of neural cells produced from a single stem cell, in part by regulating the transcription of the target genes buttonhead and pointed.

Whole-brain neural network analysis (connectomics) using cell lineage-based neuron-labeling method.

The brain is a computing machine that receives input signals from sensory neurons, calculates best responses to changing environments, and sends output signals to motor muscles. How such computation is materialized remains largely unknown. Understanding the entire wiring network of neural connections in the brain, which is recently called the connectomics (connection + omics), should provide indispensable insights on this problem.To resolve the circuit diagram from the tangled thickets of neural fibers, only a small subset of neurons should be visualized at one time. Previous studies visualized such selective cells by injecting dyes or by detecting specific molecules or gene expression patterns using antibodies and expression driver strains. These approaches were unfortunately not efficient enough for identifying all the brain cells in a comprehensive and systematic manner.Neurons are generated by neural stem cells. The entire neural population can therefore be divided into a finite number of families - or clones - of the cells that are the progeny of each single stem cell. The central brain of the fruit fly Drosophila melanogaster consists of about 15,000 neurons per side and is made by utmost 100 stem cells. By genetically labeling one of such stem cells and tracing the projection patterns of its progeny in the adult brain, we were able to identify the neural projections of almost all the clonal cell groups.To visualize these neural projections, we made serial optical sections of the fly brain using laser confocal microscopy. Because of its relatively small size (0.6-mm wide and less than 0.3-mm thick), the entire fly brain can be imaged using high-resolution objectives with n.a. 1.2. Neuronal fibers are visualized by ectopically expressed cytoplasmic and membrane-bound fluorescent proteins, and the output synaptic sites are visualized with ectopically expressed tag proteins that are fused with the proteins associated with synaptic vesicles. In addition, density of all the synapses was visualized using an antibody against synaptic proteins. Signal distributions of the latter data were put into the template using 3D non-linear elastic morphing. The data of other channels are morphed with the same formula. By doing so, neural projection data obtained from different brain samples can directly be compared in the 3D space.Neurons generated by each stem cell turned out to form lineage-specific sets of projections that arborize in distinct regions of the brain, arguably serving specific aspects of brain functions. We named such clonally associated projection units the clonal units. Different parts of the brain were formed by distinct sets of overlapping clonal units. By tracing the projections made by each clonal unit, we were able to establish a comprehensive connection diagram between different brain regions. Microscopic analysis of neuronal fibers thus leads to the understanding of the entire brain neural network.

What can fruit flies teach us about karate?

Understanding the logic behind how a fruit fly's brain tells it to groom its body parts in a stereotyped order might help us understand other behaviours that also involve a series of actions.

Turning point: Marta Zlatic

Neuroscientist reaches milestone towards fruit-fly brain map.

A Parallel Programming Model of Local Processing Units in the Fruit Fly Brain

A Parallel Programming Model of Local Processing Units in the Fruit Fly Brain