CoChat
Sign Up
Cited by 281Neurobiology and Insect Physiology ResearchMemory and Neural MechanismsNeural dynamics and brain function

Do the right thing: neural network mechanisms of memory formation, expression and update in Drosophila

Open access
Cognigni, Paola, Felsenberg, Johannes, Waddell, Scott·2018·Current Opinion in Neurobiology
DOI 10.1016/j.conb.2017.12.002PMC PMC5981003
Open this paper in CoChat — free accountOpen PDF

Abstract

When animals learn, plasticity in brain networks that respond to specific cues results in a change in the behavior that these cues elicit. Individual network components in the mushroom bodies of the fruit fly Drosophila melanogaster represent cues, learning signals and behavioral outcomes of learned experience. Recent findings have highlighted the importance of dopamine-driven plasticity and activity in feedback and feedforward connections, between various elements of the mushroom body neural network. These computational motifs have been shown to be crucial for long term olfactory memory consolidation, integration of internal states, re-evaluation and updating of learned information. The often recurrent circuit anatomy and a prolonged requirement for activity in parts of these underlying networks, suggest that self-sustained and precisely timed activity is a fundamental feature of network computations in the insect brain. Together these processes allow flies to continuously adjust the content of their learned knowledge and direct their behavior in a way that best represents learned expectations and serves their most pressing current needs.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.conb.2017.12.002

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • The authors moved the simulation framework from PyBullet to MuJoCo, a more widely used physics simulator.

    “Second, we moved the simulation framework from PyBullet to MuJoCo 45 , a more widely used physics simulator.”

    From NeuroMechFly v2: simulating embodied sensorimotor control in adult Drosophila (2024) · cites this paper as [45]

    The Introduction and Conclusions discuss neural mechanisms of memory in Drosophila, not physics simulation. Searches for PyBullet, MuJoCo, and a change of simulation framework found no relevant passage in our copy. The source therefore does not verify the cited statement. (LLM, conf=0.78)

    Experimental — accuracy not yet measured

  • FlyGym is implemented based on MuJoCo and the dm control library and complies with the Gymnasium API for MDP.

    “FlyGym is implemented based on MuJoCo 45 and the dm control 99 library and complies with the Gymnasium API for MDP 12 .”

    From NeuroMechFly v2: simulating embodied sensorimotor control in adult Drosophila (2024) · cites this paper as [45]

    The paper’s sections on mushroom-body cell types and internal-state control discuss neural circuits and fly behavior, not FlyGym software. Searches for FlyGym, MuJoCo, dm control, Gymnasium, and MDP found no passage addressing the claimed implementation or API compliance; page numbers were unavailable in our copy. (LLM, conf=0.77)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 60 · Cited by 281

Research works printed but not linked: 54

  1. [1]Quinn W.G. Harris W.A. Benzer S. Conditioned behavior in Drosophila melanogaster Proc Natl Acad Sci U S A 71 1974 708 712 4207071 PMC388082
  2. [2]Heisenberg M. Borst A. Wagner S. Byers D. Drosophila mushroom body mutants are deficient in olfactory learning J Neurogenet 2 1985 1 30 4020527
  3. [3]Tanaka N.K. Tanimoto H. Ito K. Neuronal assemblies of the Drosophila mushroom body J Comp Neurol 508 2008 711 755 18395827
  4. [6]Zheng Z. Lauritzen J.S. Perlman E. Robinson C.G. Nichols M. Milkie D. Torrens O. Price J. Fisher C.B. Sharifi N. A complete electron microscopy volume of the brain of adult Drosophila melanogaster bioRxiv 2017 PMC6063995 30033368
  5. Eichler K. Li F. Litwin-Kumar A. Park Y. Andrade I. Schneider-Mizell C.M. Saumweber T. Huser A. Eschbach C. Gerber B. The complete connectome of a learning and memory centre in an insect brain Nature 548 2017 175 182 28796202 PMC5806122 Complete reconstruction of the larval mushroom body network from an EM volume. Reveals many interesting network topologies including feedback and feedforward connectivity in the MBON network.
  6. [8]Bouzaiane E. Trannoy S. Scheunemann L. Plaçais P.-Y. Preat T. Two independent mushroom body output circuits retrieve the six discrete components of Drosophila aversive memory Cell Rep 11 2015 1280 1292 25981036
  7. Felsenberg J. Barnstedt O. Cognigni P. Lin S. Waddell S. Re-evaluation of learned information in Drosophila Nature 544 2017 240 244 28379939 PMC5392358 Characterizes the network structure of memory re-evaluation and re-consolidation in flies to reveal recurrent connections necessary to reassess and stabilize memories after exposure to stimuli previously encountered in appetitive conditioning. In memory extinction, MBON-to-DAN recurrencies recruit the aversive neural machinery to form a new, opposing memory that offsets the original, appetitive one. Memory reconsolidation also relies on MBONs sequentially recruiting multiple DAN populations.
  8. Owald D. Felsenberg J. Talbot C.B. Das G. Perisse E. Huetteroth W. Waddell S. Activity of defined mushroom body output neurons underlies learned olfactory behavior in Drosophila Neuron 86 2015 417 427 25864636 PMC4416108 This article describes glutamatergic M4/M6 MBONs to be necessary for aversive and appetitive memory retrieval. Conditioning induces bidirectional changes in the odor drive of that MBON: a decreased drive after appetitive conditioning and an increase after aversive training. Consistently, blocking these MBONs mimics appetitive conditioning, whereas activating them induces avoidance behavior.
  9. [11]Pai T.-P. Chen C.-C. Lin H.-H. Chin A.-L. Lai J.S.-Y. Lee P.-T. Tully T. Chiang A.-S. Drosophila ORB protein in two mushroom body output neurons is necessary for long-term memory formation Proc Natl Acad Sci U S A 110 2013 7898 7903 23610406 PMC3651462
  10. Perisse E. Owald D. Barnstedt O. Talbot C.B. Huetteroth W. Waddell S. Aversive learning and appetitive motivation toggle feed-forward inhibition in the Drosophila mushroom body Neuron 90 2016 1086 1099 27210550 PMC4893166 Investigation of the GABAergic MBON, MVP2, reveals its dual role in storing aversive memories and conveying the hunger state of flies. Activity of the MVP2 neurons favors the retrieval of appetitive memory by feed forward inhibition to avoidance promoting MBONs.
  11. [13]Plaçais P.-Y. Trannoy S. Friedrich A.B. Tanimoto H. Preat T. Two pairs of mushroom body efferent neurons are required for appetitive long-term memory retrieval in Drosophila Cell Rep 5 2013 769 780 24209748
  12. [14]Séjourné J. Plaçais P.-Y. Aso Y. Siwanowicz I. Trannoy S. Thoma V. Tedjakumala S.R. Rubin G.M. Tchénio P. Ito K. Mushroom body efferent neurons responsible for aversive olfactory memory retrieval in Drosophila Nat Neurosci 14 2011 903 910 21685917
  13. [15]Wu J.-K. Tai C.-Y. Feng K.-L. Chen S.-L. Chen C.-C. Chiang A.-S. Long-term memory requires sequential protein synthesis in three subsets of mushroom body output neurons in Drosophila Sci Rep 7 2017 7112 28769066 PMC5540930
  14. [16]Aso Y. Siwanowicz I. Bräcker L. Ito K. Kitamoto T. Tanimoto H. Specific dopaminergic neurons for the formation of labile aversive memory Curr Biol 20 2010 1445 1451 20637624 PMC2929706
  15. [17]Aso Y. Rubin G.M. Dopaminergic neurons write and update memories with cell-type-specific rules eLife 5 2016 e16135 27441388 PMC4987137
  16. [19]Claridge-Chang A. Roorda R.D. Vrontou E. Sjulson L. Li H. Hirsh J. Miesenböck G. Writing memories with light-addressable reinforcement circuitry Cell 139 2009 405 415 19837039 PMC3920284
  17. [20]Das G. Klappenbach M. Vrontou E. Perisse E. Clark C.M. Burke C.J. Waddell S. Drosophila learn opposing components of a compound food stimulus Curr Biol 24 2014 1723 1730 25042590 PMC4131107
  18. [21]Krashes M.J. DasGupta S. Vreede A. White B. Armstrong J.D. Waddell S. A neural circuit mechanism integrating motivational state with memory expression in Drosophila Cell 139 2009 416 427 19837040 PMC2780032
  19. [22]Liu C. Plaçais P.-Y. Yamagata N. Pfeiffer B.D. Aso Y. Friedrich A.B. Siwanowicz I. Rubin G.M. Preat T. Tanimoto H. A subset of dopamine neurons signals reward for odour memory in Drosophila Nature 488 2012 512 516 22810589
  20. [23]Schroll C. Riemensperger T. Bucher D. Ehmer J. Völler T. Erbguth K. Gerber B. Hendel T. Nagel G. Buchner E. Light-induced activation of distinct modulatory neurons triggers appetitive or aversive learning in Drosophila larvae Curr Biol 16 2006 1741 1747 16950113
  21. [24]Vasmer D. Pooryasin A. Riemensperger T. Fiala A. Induction of aversive learning through thermogenetic activation of Kenyon cell ensembles in Drosophila Front Behav Neurosci 8 2014 PMC4030157 24860455
  22. [25]Heisenberg M. Mushroom body memoir: from maps to models Nat Rev Neurosci 4 2003 266 275 12671643
  23. [26]Owald D. Waddell S. Olfactory learning skews mushroom body output pathways to steer behavioral choice in Drosophila Curr Opin Neurobiol 35 2015 178 184 26496148 PMC4835525
  24. [27]Campbell R.A.A. Honegger K.S. Qin H. Li W. Demir E. Turner G.C. Imaging a population code for odor identity in the Drosophila mushroom body J Neurosci Off J Soc Neurosci 33 2013 10568 10581 PMC3685844 23785169
  25. [28]Lin A.C. Bygrave A.M. de Calignon A. Lee T. Miesenböck G. Sparse, decorrelated odor coding in the mushroom body enhances learned odor discrimination Nat Neurosci 17 2014 559 568 24561998 PMC4000970
  26. [29]Turner G.C. Bazhenov M. Laurent G. Olfactory representations by Drosophila mushroom body neurons J Neurophysiol 99 2008 734 746 18094099
  27. [30]Aso Y. Sitaraman D. Ichinose T. Kaun K.R. Vogt K. Belliart-Guérin G. Plaçais P.-Y. Robie A.A. Yamagata N. Schnaitmann C. Mushroom body output neurons encode valence and guide memory-based action selection in Drosophila eLife 3 2014 e04580 25535794 PMC4273436
  28. Aso Y. Hattori D. Yu Y. Johnston R.M. Iyer N.A. Ngo T.-T. Dionne H. Abbott L.F. Axel R. Tanimoto H. The neuronal architecture of the mushroom body provides a logic for associative learning eLife 3 2014 e04577 25535793 PMC4273437 Comprehensively classifies the cell types that make up the mushroom body and generates precise genetic tools for their visualization and manipulation. The anatomical description identifies several feed-forward connections within the mushroom body and recurrent feedback between MBONs and DANs which connect in loops in the surrounding brain regions.
  29. [35]Waddell S. Reinforcement signalling in Drosophila; dopamine does it all after all Curr Opin Neurobiol 23 2013 324 329 23391527 PMC3887340
  30. [36]Yamagata N. Ichinose T. Aso Y. Plaçais P.-Y. Friedrich A.B. Sima R.J. Preat T. Rubin G.M. Tanimoto H. Distinct dopamine neurons mediate reward signals for short- and long-term memories Proc Natl Acad Sci U S A 112 2015 578 583 25548178 PMC4299218
  31. [37]Quinn W.G. Sziber P.P. Booker R. The Drosophila memory mutant amnesiac Nature 277 1979 212 214 121760
  32. [38]Keene A.C. Krashes M.J. Leung B. Bernard J.A. Waddell S. Drosophila dorsal paired medial neurons provide a general mechanism for memory consolidation Curr Biol 16 2006 1524 1530 16890528
  33. [39]Keene A.C. Stratmann M. Keller A. Perrat P.N. Vosshall L.B. Waddell S. Diverse odor-conditioned memories require uniquely timed dorsal paired medial neuron output Neuron 44 2004 521 533 15504331
  34. [40]Dudai Y. Sher B. Segal D. Yovell Y. Defective responsiveness of adenylate cyclase to forskolin in the Drosophila memory mutant rutabaga J Neurogenet 2 1985 365 380 3935769
  35. [41]Tempel B.L. Bonini N. Dawson D.R. Quinn W.G. Reward learning in normal and mutant Drosophila Proc Natl Acad Sci U S A 80 1983 1482 1486 6572401 PMC393622
  36. [42]Keene A.C. Waddell S. Drosophila olfactory memory: single genes to complex neural circuits Nat Rev Neurosci 8 2007 341 354 17453015
  37. [43]Krashes M.J. Keene A.C. Leung B. Armstrong J.D. Waddell S. Sequential use of mushroom body neuron subsets during Drosophila odor memory processing Neuron 53 2007 103 115 17196534 PMC1828290
  38. [44]Tully T. Preat T. Boynton S.C. Del Vecchio M. Genetic dissection of consolidated memory in Drosophila Cell 79 1994 35 47 7923375
  39. [45]Krashes M.J. Waddell S. Rapid consolidation to a radish and protein synthesis-dependent long-term memory after single-session appetitive olfactory conditioning in Drosophila J Neurosci Off J Soc Neurosci 28 2008 3103 3113 PMC2516741 18354013
  40. [46]Colomb J. Kaiser L. Chabaud M.-A. Preat T. Parametric and genetic analysis of Drosophila appetitive long-term memory and sugar motivation Genes Brain Behav 8 2009 407 415 19220480
  41. [47]Cervantes-Sandoval I. Davis R.L. Distinct traces for appetitive versus aversive olfactory memories in DPM neurons of Drosophila Curr Biol 22 2012 1247 1252 22658595 PMC3396741
  42. [48]Pitman J.L. Huetteroth W. Burke C.J. Krashes M.J. Lai S.-L. Lee T. Waddell S. A pair of inhibitory neurons are required to sustain labile memory in the Drosophila mushroom body Curr Biol 21 2011 855 861 21530258 PMC3111962
  43. [49]Yu D. Keene A.C. Srivatsan A. Waddell S. Davis R.L. Drosophila DPM neurons form a delayed and branch-specific memory trace after olfactory classical conditioning Cell 123 2005 945 957 16325586
  44. Ichinose T. Aso Y. Yamagata N. Abe A. Rubin G.M. Tanimoto H. Reward signal in a recurrent circuit drives appetitive long-term memory formation eLife 4 2015 PMC4643015 26573957 Identifies the α1 compartment as a crucial location for the formation, consolidation and retrieval of long-term appetitive olfactory memory and postulates a possible feedback loop between the α1 MBONs and the α1 DANs, suggesting that recurrent activity in this circuit may stabilize memory for long-term storage.
  45. [51]Burke C.J. Waddell S. Remembering nutrient quality of sugar in Drosophila Curr Biol 21 2011 746 750 21514159 PMC3094154
  46. [52]Huetteroth W. Perisse E. Lin S. Klappenbach M. Burke C. Waddell S. Sweet taste and nutrient value subdivide rewarding dopaminergic neurons in Drosophila Curr Biol 25 2015 751 758 25728694 PMC4372253
  47. Musso P.-Y. Tchenio P. Preat T. Delayed dopamine signaling of energy level builds appetitive long-term memory in Drosophila Cell Rep 10 2015 1023 1031 25704807 Separates the gustatory and energetic components of a sugar reward in time to describe a circuit for the stepwise construction of long term appetitive memory that is gated by the MP1 dopaminergic neurons. These neurons display oscillatory patterns of activity, which could arise from recurrent circuits modulated by internal state.
  48. [54]Plaçais P.-Y. Trannoy S. Isabel G. Aso Y. Siwanowicz I. Belliart-Guérin G. Vernier P. Birman S. Tanimoto H. Preat T. Slow oscillations in two pairs of dopaminergic neurons gate long-term memory formation in Drosophila Nat Neurosci 15 2012 592 599 22366756
  49. [55]Lin S. Owald D. Chandra V. Talbot C. Huetteroth W. Waddell S. Neural correlates of water reward in thirsty Drosophila Nat Neurosci 17 2014 1536 1542 25262493 PMC4213141
  50. [56]Lewis L.P.C. Siju K.P. Aso Y. Friedrich A.B. Bulteel A.J.B. Rubin G.M. Grunwald Kadow I.C. A higher brain circuit for immediate integration of conflicting sensory information in Drosophila Curr Biol 25 2015 2203 2214 26299514
  51. Hattori D. Aso Y. Swartz K.J. Rubin G.M. Abbott L.F. Axel R. Representations of novelty and familiarity in a mushroom body compartment Cell 169 2017 956-969.e17 PMC5806120 28502772 Describes a specific MBON, the α′3 MBON, which responds to novel odors but suppresses its activity to familiar odors. This is linked to a behavioral response: if presented with a novel odor, but not a familiar one, flies stop grooming. By manipulating the α′3 MBON during this grooming assay, the behavioral response to a novel odor can be either facilitated or reduced.
  52. [58]Lagasse F. Devaud J.-M. Mery F. A switch from cycloheximide-resistant consolidated memory to cycloheximide-sensitive reconsolidation and extinction in Drosophila J Neurosci Off J Soc Neurosci 29 2009 2225 2230 PMC6666331 19228975
  53. [59]Nader K. Reconsolidation and the dynamic nature of memory Cold Spring Harb Perspect Biol 7 2015 a021782 26354895 PMC4588064
  54. [60]Cervantes-Sandoval I. Phan A. Chakraborty M. Davis R.L. Reciprocal synapses between mushroom body and dopamine neurons form a positive feedback loop required for learning eLife 6 2017 PMC5425253 28489528

Authors
Cognigni, P., Felsenberg, J., & Waddell, S.
Affiliations
University of Oxford (GB)
Corresponding author
Waddell, Scott
ORCID
Venue
Current Opinion in Neurobiology
Publisher
Elsevier BV
Published
2018-04
Volume
49
Pages
51-58
ISSN
0959-4388 (ISSN-L)
DOI
10.1016/j.conb.2017.12.002
PMC
PMC5981003
OpenAlex
W2774719659
Cited by
281
References
60
Citations by year
2026: 19 · 2025: 28 · 2024: 41 · 2023: 32 · 2022: 34 · 2021: 36 · 2020: 36 · 2019: 33 · 2018: 22
FWCI
3.07
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Opinion in Neurobiology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • Deutsche Forschungsgemeinschaft (FE 1563/1-1)
  • Gatsby Charitable Foundation and Bettencourt–Schueller Foundation
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
Keywords
Drosophila melanogaster, mushroom body, olfactory memory, memory consolidation, memory updating, recurrent neural circuits, memory expression, neural network computation
MeSH terms
Animals, Brain, Computer Simulation, Drosophila, Learning, Models, Neurological, Neural Pathways, Neurons

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review