scholarly journals A linear neural circuit for light avoidance in Drosophila larvae

2021 ◽  
Author(s):  
Altar Sorkaç ◽  
Yiannis A. Savva ◽  
Doruk Savaş ◽  
Mustafa Talay ◽  
Gilad Barnea
Keyword(s):  
Neural Circuit ◽  
Fruit Fly ◽  
Neuroendocrine Cells ◽  
Avoidance Behaviour ◽  
Combined Approach ◽  
Epistasis Analysis ◽  
Neuronal Inhibition ◽  
Neuronal Types ◽  
Light Avoidance ◽  
Functional Analyses

AbstractUnderstanding how neural circuits underlie behaviour is challenging even in the era of the connectome because it requires a combined approach encompassing anatomical and functional analyses. This is exemplified in studying the circuit underlying the light-avoidance behaviour displayed by the larvae of the fruit fly Drosophila melanogaster. While this behaviour is robust and the nervous system relatively simple, only bits and pieces of the circuit have been delineated1. Indeed, some studies resulted in contradicting conclusions regarding the contributions of various neuronal types to this behaviour2,3. Here we devise trans-Tango MkII, a new version of the transsynaptic circuit tracing and manipulation tool trans-Tango4. We implement trans-Tango MkII in anatomical tracing and combine it with circuit epistasis analysis. We use neuronal inhibition to test necessity of particular neuronal types for light-avoidance. We complement these experiments by selective neuronal activation to examine sufficiency in rescuing light-avoidance deficiencies exhibited by photoreceptor mutants. Together, our studies reveal a four-order, linear circuit for light-avoidance behaviour connecting the light-detecting photoreceptors with a pair of neuroendocrine cells via two types of clock neurons. Our combined approach could be readily expanded to other larval circuits. Further, this strategy provides the framework for studying more complex nervous systems and behaviours.

scholarly journals Drosophila carboxypeptidase D (SILVER) is a key enzyme in neuropeptide processing required to maintain locomotor activity levels and survival rate

2019 ◽  
Author(s):  
Dennis Pauls ◽  
Yasin Hamarat ◽  
Luisa Trufasu ◽  
Tim M. Schendzielorz ◽  
Gertrud Gramlich ◽  
...  
Keyword(s):  
Survival Rate ◽  
Fruit Fly ◽  
Neuroendocrine Cells ◽  
Phylogenomic Analysis ◽  
Activity Levels ◽  
Peptidergic Neurons ◽  
Adipokinetic Hormone ◽  
Hypomorphic Mutation ◽  
Key Enzyme ◽  
Carboxypeptidase D

AbstractNeuropeptides are processed from larger preproproteins by a dedicated set of enzymes. The molecular and biochemical mechanisms underlying preproprotein processing and the functional importance of processing enzymes are well characterised in mammals, but little studied outside this group. In contrast to mammals, Drosophila lacks a gene for carboxypeptidase E (CPE), a key enzyme for mammalian peptide processing.By combining peptidomics and neurogenetics, we addressed the role of Drosophila carboxypeptidase D (dCPD) in global neuropeptide processing and selected peptide-regulated behaviours. We found that a deficiency in dCPD results in C-terminally extended peptides across the peptidome, suggesting that dCPD took over CPE function in the fruit fly. dCPD is widely expressed throughout the nervous system, including peptidergic neurons in the mushroom body and neuroendocrine cells expressing adipokinetic hormone. Conditional hypomorphic mutation in the dCPD-encoding gene silver in the larva causes lethality, and leads to deficits in adult starvation-induced hyperactivity and appetitive gustatory preference, as well as to reduced survival rate and activity levels. A phylogenomic analysis suggests that loss of CPE is not a common insect feature, but specifically occured in Hymenoptera and Diptera. Our results show that dCPD is a key enzyme for neuropeptide processing in Drosophila, and is required for proper peptide-regulated behaviour. dCPD thus appears as a suitable target to genetically shut down total neuropeptide production in peptidergic neurons. Our results raise the question why Drosophila and other Diptera and Hymenoptera –unlike other insects-have obviously lost the gene for CPE but kept a gene encoding CPD.

scholarly journals Idiosyncratic learning performance in flies generalizes across modalities

2021 ◽  
Author(s):  
Matthew Smith ◽  
Kyle S. Honegger ◽  
Glenn Turner ◽  
Benjamin de Bivort
Keyword(s):  
Individual Differences ◽  
Neural Circuit ◽  
Bitter Taste ◽  
Model Organism ◽  
Fruit Fly ◽  
Learning Performance ◽  
Suitable Model ◽  
Mechanistic Basis ◽  
Innate Behaviors ◽  
Stimulus Modalities

AbstractIndividuals vary in their innate behaviors, even when they have the same genome and have been reared in the same environment. The extent of individuality in plastic behaviors, like learning, is less well characterized. Also unknown is the extent to which intragenotypic differences in learning generalize: if an individual performs well in one assay, will it perform well in other assays? We investigated this using the fruit fly Drosophila melanogaster, an organism long-used to study the mechanistic basis of learning and memory. We found that isogenic flies, reared in identical lab conditions, and subject to classical conditioning that associated odorants with electric shock, exhibit clear individuality in their learning responses. Flies that performed well when an odor was paired with shock tended to perform well when other odors were paired with shock, or when the original odor was paired with bitter taste. Thus, individuality in learning performance appears to be prominent in isogenic animals reared identically, and individual differences in learning performance generalize across stimulus modalities. Establishing these results in flies opens up the possibility of studying the genetic and neural circuit basis of individual differences in learning in a highly suitable model organism.

scholarly journals Multiple neurons encode CrebB dependent appetitive long-term memory in the mushroom body circuit

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Yves F Widmer ◽  
Cornelia Fritsch ◽  
Magali M Jungo ◽  
Silvia Almeida ◽  
Boris Egger ◽  
...  
Keyword(s):  
Mushroom Body ◽  
Neural Circuit ◽  
Fruit Fly ◽  
Conditional Knockout ◽  
Long Term Memory ◽  
Temporal Precision ◽  
Regulatory Changes ◽  
Transcriptional Memory ◽  
Knockout Allele

Lasting changes in gene expression are critical for the formation of long-term memories (LTMs), depending on the conserved CrebB transcriptional activator. While requirement of distinct neurons in defined circuits for different learning and memory phases have been studied in detail, only little is known regarding the gene regulatory changes that occur within these neurons. We here use the fruit fly as powerful model system to study the neural circuits of CrebB-dependent appetitive olfactory LTM. We edited the CrebB locus to create a GFP-tagged CrebB conditional knockout allele, allowing us to generate mutant, post-mitotic neurons with high spatial and temporal precision. Investigating CrebB-dependence within the mushroom body (MB) circuit we show that MB α/β and α’/β’ neurons as well as MBON α3, but not in dopaminergic neurons require CrebB for LTM. Thus, transcriptional memory traces occur in different neurons within the same neural circuit.

scholarly journals Mysterious inhibitory cell regulator investigated and found likely to be secretogranin II related

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3833 ◽  
Author(s):  
John E. Hart ◽  
Iain J. Clarke ◽  
Gail P. Risbridger ◽  
Ben Ferneyhough ◽  
Mónica Vega-Hernández
Keyword(s):  
Bone Marrow Cells ◽  
Protein A ◽  
Fruit Fly ◽  
Neuroendocrine Cells ◽  
Terminal Sequence ◽  
Compensatory Renal Growth ◽  
Tissue Mass ◽  
Secretogranin Ii

In the context of a hunt for a postulated hormone that is tissue-mass inhibiting and reproductively associated, there is described probable relatedness to a granin protein. A 7–8 kDa polypeptide candidate (gels/MS) appeared in a bioassay-guided fractionation campaign involving sheep plasma. An N-terminal sequence of 14 amino acids was obtained for the polypeptide by Edman degradation. Bioinformatics and molecular biology failed to illuminate any ovine or non-ovine protein which might relate to this sequence. The N-terminal sequence was synthesized as the 14mer EPL001 peptide and surprisingly found to be inhibitory in an assay in vivo of compensatory renal growth in the rat and modulatory of nematode fecundity, in line with the inhibitory hormone hypothesis. Antibodies were raised to EPL001 and their deployment upheld the hypothesis that the EPL001 amino acid sequence is meaningful and relevant, notwithstanding bioinformatic obscurity. Immunohistochemistry (IHC) in sheep, rodents and humans yielded staining of seeming endocrine relevance (e.g. hypothalamus, gonads and neuroendocrine cells in diverse tissues), with apparent upregulation in certain human tumours (e.g. pheochromocytoma). Discrete IHC staining in Drosophila melanogaster embryo brain was seen in glia and in neuroendocrine cells, with staining likely in the corpus cardiacum. The search for the endogenous antigen involved immunoprecipitation (IP) followed by liquid chromatography and mass spectrometry (LC–MS). Feedstocks were PC12 conditioned medium and aqueous extract of rat hypothalamus—both of which had anti-proliferative and pro-apoptotic effects in an assay in vitro involving rat bone marrow cells, which inhibition was subject to prior immunodepletion with an anti-EPL001 antibody—together with fruit fly embryo material. It is concluded that the mammalian antigen is likely secretogranin II (SgII) related. The originally seen 7–8 kDa polypeptide is suggested to be a new proteoform of secretogranin II of ∼70 residues, SgII-70, with the anti-EPL001 antibody seeing a discontinuous epitope. The fly antigen is probably Q9W2X8 (UniProt), an uncharacterised protein newly disclosed as a granin and provisionally dubbed macrogranin I (MgI). SgII and Q9W2X8 merit further investigation in the context of tissue-mass inhibition.

scholarly journals Light, heat, action: neural control of fruit fly behaviour

2015 ◽  
Vol 370 (1677) ◽  
pp. 20140211 ◽  
Author(s):  
David Owald ◽  
Suewei Lin ◽  
Scott Waddell
Keyword(s):  
Drosophila Melanogaster ◽  
Neural Activity ◽  
Neural Control ◽  
Neural Circuit ◽  
Cell Signalling ◽  
Fruit Fly ◽  
Signalling Pathways ◽  
Holistic View ◽  
Cellular Resolution ◽  
Technical Advances

The fruit fly Drosophila melanogaster has emerged as a popular model to investigate fundamental principles of neural circuit operation. The sophisticated genetics and small brain permit a cellular resolution understanding of innate and learned behavioural processes. Relatively recent genetic and technical advances provide the means to specifically and reproducibly manipulate the function of many fly neurons with temporal resolution. The same cellular precision can also be exploited to express genetically encoded reporters of neural activity and cell-signalling pathways. Combining these approaches in living behaving animals has great potential to generate a holistic view of behavioural control that transcends the usual molecular, cellular and systems boundaries. In this review, we discuss these approaches with particular emphasis on the pioneering studies and those involving learning and memory.

scholarly journals Neural circuit evolved to process pheromone differently in two species of fruit fly

Nature ◽  
2018 ◽  
Vol 559 (7715) ◽  
pp. 485-487
Author(s):  
Nicolas Gompel ◽  
Benjamin Prud’homme
Keyword(s):  
Neural Circuit ◽  
Fruit Fly

scholarly journals A higher-order configuration of the heterodimeric DOT1L–AF10 coiled-coil domains potentiates their leukemogenenic activity

2019 ◽  
Vol 116 (40) ◽  
pp. 19917-19923 ◽  
Author(s):  
Xiaosheng Song ◽  
Liuliu Yang ◽  
Mingzhu Wang ◽  
Yue Gu ◽  
Buqing Ye ◽  
...  
Keyword(s):  
Leucine Zipper ◽  
Coiled Coil ◽  
Binding Mode ◽  
Chromosomal Translocations ◽  
Chimeric Proteins ◽  
Binary Complex ◽  
Combined Approach ◽  
Terminal Portion ◽  
Interaction Sites ◽  
Functional Analyses

Chromosomal translocations of MLL1 (Mixed Lineage Leukemia 1) yield oncogenic chimeric proteins containing the N-terminal portion of MLL1 fused with distinct partners. The MLL1–AF10 fusion causes leukemia through recruiting the H3K79 histone methyltransferase DOT1L via AF10’s octapeptide and leucine zipper (OM-LZ) motifs. Yet, the precise interaction sites in DOT1L, detailed interaction modes between AF10 and DOT1L, and the functional configuration of MLL1–AF10 in leukeomogenesis remain unknown. Through a combined approach of structural and functional analyses, we found that the LZ domain of AF10 interacts with the coiled-coil domains of DOT1L through a conserved binding mode and discovered that the C-terminal end of the LZ domain and the OM domain of AF10 mediate the formation of a DOT1L–AF10 octamer via tetramerization of the binary complex. We reveal that the oligomerization ability of the DOT1L–AF10 complex is essential for MLL1–AF10’s leukemogenic function. These findings provide insights into the molecular basis of pathogenesis by MLL1 rearrangements.

scholarly journals The Drosophila Larval Locomotor Circuit Provides a Model to Understand Neural Circuit Development and Function

2021 ◽  
Vol 15 ◽  
Author(s):  
Iain Hunter ◽  
Bramwell Coulson ◽  
Aref Arzan Zarin ◽  
Richard A. Baines
Keyword(s):  
Neural Circuits ◽  
Neural Circuit ◽  
Fruit Fly ◽  
Model Organisms ◽  
Generic Model ◽  
Critical Periods ◽  
Neuroscience Research ◽  
Circuit Development ◽  
And Function ◽  
Model Circuit

It is difficult to answer important questions in neuroscience, such as: “how do neural circuits generate behaviour?,” because research is limited by the complexity and inaccessibility of the mammalian nervous system. Invertebrate model organisms offer simpler networks that are easier to manipulate. As a result, much of what we know about the development of neural circuits is derived from work in crustaceans, nematode worms and arguably most of all, the fruit fly, Drosophila melanogaster. This review aims to demonstrate the utility of the Drosophila larval locomotor network as a model circuit, to those who do not usually use the fly in their work. This utility is explored first by discussion of the relatively complete connectome associated with one identified interneuron of the locomotor circuit, A27h, and relating it to similar circuits in mammals. Next, it is developed by examining its application to study two important areas of neuroscience research: critical periods of development and interindividual variability in neural circuits. In summary, this article highlights the potential to use the larval locomotor network as a “generic” model circuit, to provide insight into mammalian circuit development and function.

scholarly journals Activity of the C. elegans egg-laying behavior circuit is controlled by competing activation and feedback inhibition

2016 ◽  
Author(s):  
Kevin M. Collins ◽  
Addys Bode ◽  
Robert W. Fernandez ◽  
Jessica E. Tanis ◽  
Jacob Brewer ◽  
...  
Keyword(s):  
Motor Neurons ◽  
Neural Circuit ◽  
Feedback Inhibition ◽  
Rhythmic Activity ◽  
Egg Laying ◽  
The Body ◽  
Active State ◽  
Neuroendocrine Cells ◽  
C Elegans ◽  
Discrete Signals

AbstractLike many behaviors, Caenorhabditis elegans egg laying alternates between inactive and active states. To understand how the underlying neural circuit turns the behavior on and off, we optically recorded circuit activity in behaving animals while manipulating circuit function using mutations, optogenetics, and drugs. In the active state, the circuit shows rhythmic activity phased with the body bends of locomotion. The serotonergic HSN command neurons initiate the active state, but accumulation of unlaid eggs also promotes the active state independent of the HSNs. The cholinergic VC motor neurons slow locomotion during egg-laying muscle contraction and egg release. The uv1 neuroendocrine cells mechanically sense passage of eggs through the vulva and release tyramine to inhibit egg laying, in part via the LGC-55 tyramine-gated Cl− channel on the HSNs. Our results identify discrete signals that entrain or detach the circuit from the locomotion central pattern generator to produce active and inactive states.

scholarly journals Trans-synaptic Fish-lips Signaling Prevents Misconnections between Non-synaptic Partner Olfactory Neurons

2019 ◽  
Author(s):  
Qijing Xie ◽  
Bing Wu ◽  
Jiefu Li ◽  
Hongjie Li ◽  
David J Luginbuhl ◽  
...  
Keyword(s):  
Olfactory Receptor ◽  
Neural Circuit ◽  
Transmembrane Protein ◽  
Fruit Fly ◽  
Projection Neuron ◽  
Olfactory Receptor Neuron ◽  
Projection Neurons ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
Circuit Assembly

AbstractOur understanding of the mechanisms of neural circuit assembly is far from complete. Identification of new wiring molecules with novel mechanisms of action will provide new insights into how complex and heterogeneous neural circuits assemble during development. Here, we performed an RNAi screen for cell-surface molecules and identified the leucine-rich-repeat containing transmembrane protein, Fish-lips (Fili), as a novel wiring molecule in the assembly of the Drosophila olfactory circuit. Fili contributes to the precise targeting of both olfactory receptor neuron (ORN) axons as well as projection neuron (PN) dendrites. Cell-type-specific expression and genetic analyses suggest that Fili sends a trans-synaptic repulsive signal to neurites of non-partner classes that prevent their targeting to inappropriate glomeruli in the antennal lobe.Significance StatementIn the fruit fly olfactory system, 50 classes of olfactory receptor neurons (ORNs) make precise synaptic connections with 50 classes of corresponding projection neurons (PNs). Identification of wiring molecules in this circuit can provide insight into understanding neural circuit assembly. This paper reports the role of a transmembrane protein, Fish-lips (Fili), in forming specific connections in this circuit. We found that some ORN axons are repelled by Fili, which is present on dendrites of non-matching PN class, preventing them from targeting inappropriate glomeruli. Similarly, some PN dendrites are repelled by Fili expressed by non-matching ORN class for their correct targeting. Together, these results suggest that Fili mediates repulsion between axons and dendrites of non-synaptic partners to ensure precise wiring patterns.

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