The interruptive effect of electric shock on odor response requires mushroom bodies in Drosophila melanogaster

2018 ◽  
Vol 18 (2) ◽  
pp. e12488
Author(s):  
W. Song ◽  
L. Zhao ◽  
Y. Tao ◽  
X. Guo ◽  
J. Jia ◽  
...  
2021 ◽  
Author(s):  
Evripidis Gkanias ◽  
Li Yan McCurdy ◽  
Michael N Nitabach ◽  
Barbara Webb

Insects adapt their response to stimuli, such as odours, according to their pairing with positive or negative reinforcements, such as sugar or shock. Recent electrophysiological and imaging findings in Drosophila melanogaster allow detailed examination of the neural mechanisms supporting acquisition, forgetting, and assimilation of memories. Drawing on this data, we identify a series of microcircuits within the mushroom bodies that reveal, for each motivational state, three different roles of dopaminergic and mushroom body output neurons in the memory dynamics. These microcircuits share components and form a unified system for rapid memory acquisition, transfer from short-term to long-term, and exploration/exploitation trade-off. We show that combined with a novel biologically plausible learning rule, a computational model of the full circuit reproduces the observed changes in the activity of each of these neurons in conditioning paradigms and can be used for flexible behavioural control.


2018 ◽  
Author(s):  
Chad A. Highfill ◽  
Brandon M. Baker ◽  
Stephenie D. Stevens ◽  
Robert R. H. Anholt ◽  
Trudy F. C. Mackay

ABSTRACTIllicit use of psychostimulants, such as cocaine and methamphetamine, constitutes a significant public health problem. Whereas neural mechanisms that mediate the effects of these drugs are well-characterized, genetic factors that account for individual variation in susceptibility to substance abuse and addiction remain largely unknown. Drosophila melanogaster can serve as a translational model for studies on substance abuse, since flies have a dopamine transporter that can bind cocaine and methamphetamine, and exposure to these compounds elicits effects similar to those observed in people, suggesting conserved evolutionary mechanisms underlying drug responses. Here, we used the D. melanogaster Genetic Reference Panel to investigate the genetic basis for variation in psychostimulant drug consumption, to determine whether similar or distinct genetic networks underlie variation in consumption of cocaine and methamphetamine, and to assess the extent of sexual dimorphism and effect of genetic context on variation in voluntary drug consumption. Quantification of natural genetic variation in voluntary consumption, preference, and change in consumption and preference over time for cocaine and methamphetamine uncovered significant genetic variation for all traits, including sex-, exposure-and drug-specific genetic variation. Genome wide association analyses identified both shared and drug-specific candidate genes, which could be integrated in genetic interaction networks. We assessed the effects of ubiquitous RNA interference (RNAi) on consumption behaviors for 34 candidate genes: all affected at least one behavior. Finally, we utilized RNAi knockdown in the nervous system to implicate dopaminergic neurons and the mushroom bodies as part of the neural circuitry underlying experience-dependent development of drug preference.AUTHOR SUMMARYIllicit use of cocaine and methamphetamine is a major public health problem. Whereas the neurological effects of these drugs are well characterized, it remains challenging to determine genetic risk factors for substance abuse in human populations. The fruit fly, Drosophila melanogaster, presents an excellent model for identifying evolutionarily conserved genes that affect drug consumption, since genetic background and exposure can be controlled precisely. We took advantage of natural variation in a panel of inbred wild derived fly lines with complete genome sequences to assess the extent of genetic variation among these lines for voluntary consumption of cocaine and methamphetamine and to explore whether some genetic backgrounds might show experience-dependent development of drug preference. The drug consumption traits were highly variable among the lines with strong sex-, drug- and exposure time-specific components. We identified candidate genes and gene networks associated with variation in consumption of cocaine and methamphetamine and development of drug preference. Using tissue-specific suppression of gene expression, we were able to functionally implicate candidate genes that affected at least one consumption trait in at least one drug and sex. In humans, the mesolimbic dopaminergic projection plays a role in drug addiction. We asked whether in Drosophila the mushroom bodies could play an analogous role, as they are integrative brain centers associated with experience-dependent learning. Indeed, our results suggest that variation in consumption and development of preference for both cocaine and methamphetamine is mediated, at least in part, through a neural network that comprises dopaminergic projections to the mushroom bodies.


2020 ◽  
Author(s):  
Marco Stucchi

ABSTRACTThe development of models of brain function remains a complex problem given the difficulty of extracting organizational principles from observations on a variety of morphologically and physiologically different neurons. State of the art results in this modeling research have been obtained by a different route, by leveraging the power of deep learning. However, this approach takes advantage of neuroscientific knowledge only to a limited extent. Here, I adopt a perspective that aims at combining experimental data and optimization algorithms by framing this modeling research as an inverse problem. To illustrate the method, I collected calcium imaging data from the first two regions of the olfactory processing pathway of the fruit fly Drosophila melanogaster, the antennal lobe and the calix of the mushroom bodies. In each case, our method gives accurate predictions for large fractions of recorded glomeruli and neurons, and the inferred networks recover known features of the biological counterpart.


Genetics ◽  
1984 ◽  
Vol 106 (4) ◽  
pp. 613-623
Author(s):  
Donald A Gailey ◽  
F Rob Jackson ◽  
Richard W Siegel

ABSTRACT One aspect of courtship in male Drosophila melanogaster has been reported to be experience dependent. Males that have courted fertilized females are virtually unresponsive to virgin females for 2-3 hr. Here, this response was utilized as an assay for the effects of conditioning mutations on experience-dependent courtship. Seven strains expressing conditioning mutations (previously isolated and characterized for learning or memory defects in an electrical shock-odor association paradigm, independent of courtship) were all found to be mutant in expression of this experience-dependent change in courtship behavior. By comparison, three control strains that were unselected for conditioning defects all expressed normal experience-dependent courtship. Other results indicate that males of the conditioning-defective strains are able to elicit necessary cues from fertilized females, yet do not then modify their courtship with virgin females. Thus, it is suggested that experience-dependent modification of courtship and the previously reported associative olfactory conditioning with electric shock share common elements of processing. The possibility that experience-dependent courtship represents adaptive behavior is discussed.


2002 ◽  
Vol 205 (9) ◽  
pp. 1233-1240 ◽  
Author(s):  
Andrea Baier ◽  
Britta Wittek ◽  
Björn Brembs

SUMMARYWe report here the effects of several neurobiological determinants on aggressive behaviour in the fruitfly Drosophila melanogaster. This study combines behavioural, transgenic, genetic and pharmacological techniques that are well established in the fruitfly, in the novel context of the neurobiology of aggression. We find that octopamine, dopamine and a region in the Drosophila brain called the mushroom bodies, all profoundly influence the expression of aggressive behaviour. Serotonin had no effect. We conclude that Drosophila, with its advanced set of molecular tools and its behavioural richness, has the potential to develop into a new model organism for the study of the neurobiology of aggression.


PLoS ONE ◽  
2015 ◽  
Vol 10 (5) ◽  
pp. e0126986 ◽  
Author(s):  
Mirjam Appel ◽  
Claus-Jürgen Scholz ◽  
Tobias Müller ◽  
Marcus Dittrich ◽  
Christian König ◽  
...  

1998 ◽  
Vol 5 (1) ◽  
pp. 157-165 ◽  
Author(s):  
Wendi S. Neckameyer

Depletion of dopamine in Drosophila melanogaster adult males, accomplished through systemic introduction of the tyrosine hydroxylase inhibitor 3-iodo-tyrosine, severely impaired the ability of these flies to modify their courtship responses to immature males. Mature males, when first exposed to immature males, will perform courtship rituals; the intensity and duration of this behavior rapidly diminshes with time. Dopamine is also required for normal female sexual receptivity; dopamine-depleted females show increased latency to copulation. One kilobase of 5′ upstream information from theDrosophila tyrosine hydroxylase (DTH) gene, when fused to theEscherichia coli β-galactosidase reporter and transduced into the genome of Drosophila melanogaster, is capable of directing expression of the reporter gene in the mushroom bodies, which are believed to mediate learning acquisition and memory retention in flies. Ablation of mushroom bodies by treatment of newly hatched larva with hydroxyurea resulted in the inability of treated mature adult males to cease courtship when placed with untreated immature males. However, functional mushroom bodies were not required for the dopaminergic modulation of an innate behavior, female sexual receptivity. These data suggest that dopamine acts as a signaling molecule within the mushroom bodies to mediate a simple form of learning.


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