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Mushroom body memoir: from maps to models

Key Points

  • Since their discovery, the mushroom bodies of the insect brain have been assumed to be involved in cognitive processing. Genetic intervention in the fly Drosophila melanogaster has provided strong evidence that they are the seat of a memory trace for odours.

  • This localization of the 'engram' to a single layer of synapses allows us to design a simple circuit model of odour memory based on the functional anatomy of the olfactory system. In the model, complex odour mixtures are assumed to be represented by neuronal activity in sets of intrinsic mushroom body neurons (Kenyon cells). Conditioning renders an extrinsic mushroom-body output neuron (CR neuron) specifically responsive to such a set (and hence to the respective odour).

  • The localization of the memory trace for odours is based on the assumption that associative olfactory learning is mediated by synpatic plasticity. Evidence that the memory trace is represented by the output synapses of Kenyon cells relies on three findings. First, the mushroom bodies are necessary for olfactory learning. Second, in many animals (molluscs, mammals), cyclic AMP signalling is crucial for synaptic plasticity. In the fly, this has been confirmed for the larval neuromuscular junction. Third, in Drosophila several genes involved in cAMP regulation are required for olfactory learning and memory. They are all preferentially expressed in the mushroom bodies, some of them specifically in the mushroom body lobes (output region). One of them, rutabaga, has been shown to be required for olfactory learning exclusively in a set of about 700 Kenyon cells. Another one, amnesiac, reveals that cAMP regulation is required for olfactory learning only during the learning experiment (rather than during development of the mushroom bodies). The output of the Kenyon cell synapses can be blocked while they are modulated, and the memory can still be retrieved later.

  • Mushroom bodies have other functions that are less understood. They seem to be involved in 'decision making', they regulate the perseverence of behaviour and they protect visual memories against context changes. A future circuit model that also addresses these functions might throw light on the basic operating principles of the brain.

Abstract

Genetic intervention in the fly Drosophila melanogaster has provided strong evidence that the mushroom bodies of the insect brain act as the seat of a memory trace for odours. This localization gives the mushroom bodies a place in a network model of olfactory memory that is based on the functional anatomy of the olfactory system. In the model, complex odour mixtures are assumed to be represented by activated sets of intrinsic mushroom body neurons. Conditioning renders an extrinsic mushroom-body output neuron specifically responsive to such a set. Mushroom bodies have a second, less understood function in the organization of the motor output. The development of a circuit model that also addresses this function might allow the mushroom bodies to throw light on the basic operating principles of the brain.

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Figure 1: Drosophila brain shown in the head capsule.
Figure 2: Olfactory pathway.
Figure 3: Circuit model of odour memory.
Figure 4: Presynaptic modulation of transmission at Kenyon cell-to-output neuron synapses is thought to underlie short- and middle-term memory of odours in flies.
Figure 5: Memory phases after electric-shock conditioning.

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References

  1. Strausfeld, N. J., Hansen, L., Li, Y., Gomez, R. S. & Ito, K. Evolution, discovery, and interpretations of arthropod mushroom bodies. Learn. Mem. 5, 11–37 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Heisenberg, M. What do the mushroom bodies do for the insect brain? Learn. Mem. 5, 1–10 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Zars, T. Behavioral functions of the insect mushroom bodies. Curr. Opin. Neurobiol. 10, 790–795 (2000).

    Article  CAS  Google Scholar 

  4. Davis, R. L. Mushroom bodies and Drosophila learning. Neuron 11, 1–14 (1993).

    Article  CAS  Google Scholar 

  5. Wong, A. M., Wang, J. W. & Axel, R. Spatial representation of the glomerular map in the Drosophila protocerebrum. Cell 109, 229–241 (2002).

    Article  CAS  Google Scholar 

  6. Marin, E. -G., Jefferis, G. S., Komiyama, T., Zhu, H. & Luo, L. Representation of the glomerular map in the Drosophila brain. Cell 109, 243–255 (2002).

    Article  CAS  Google Scholar 

  7. Mobbs, P. G. The brain of the honeybee Apis mellifera. I. The connections and spatial organization of the mushroom bodies. Phil. Trans. R. Soc. Lond. B 298, 309–354 (1982).

    Article  Google Scholar 

  8. Schürmann, F. -W. in Arthropod Brains: Evolution, Development, Structure, and Function (ed. Gupta, A. P.) (John Wiley & Sons, New York, 1987).

    Google Scholar 

  9. Ito, K. et al. The organization of extrinsic neurons and their implications in the functional roles of the mushroom bodies in Drosophila melanogaster Meigen. Learn. Mem. 5, 52–77 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Strausfeld, N. J., Vilinsky, I. & Sinakevitch, I. The mushroom bodies of Drosophila melanogaster: an immunocytological and Golgi study of Kenyon cell organization in the Calyces and lobes. Microsc. Tech. (in the press).

  11. Strausfeld, N. J. & Li, Y. -S. Representation of the calyces in the medial and vertical lobes of cockroach mushroom bodies. J. Comp. Neurol. 409, 626–646 (1999).

    Article  CAS  Google Scholar 

  12. Strausfeld, N. Organization of the honey bee mushroom body: representation of the calyx within the vertical and gamma lobes. J. Comp. Neurol. 450, 4–33 (2002).

    Article  Google Scholar 

  13. Lee, T., Lee, A. & Luo, L. Development of the Drosophila mushroom bodies: sequential generation of three distinct types of neurons from a neuroblast. Development 126, 4065–4076 (1999).

    CAS  PubMed  Google Scholar 

  14. Vosshall, L. B., Wong, A. M. & Axel, R. An olfactory sensory map in the fly brain. Cell 102, 147–159 (2000).

    Article  CAS  Google Scholar 

  15. Borst, A. Computation of olfactory signals in Drosophila melanogaster. J. Comp. Physiol. A. 152, 373–383 (1983). The study demonstrates narrow-range odour concentration invariance in behaviour and offers a quantitative model that might be realized in the antennal lobe.

    Article  Google Scholar 

  16. Sachse, S. & Galizia, C. G. Role of inhibition for temporal and spatial odor representation in olfactory output neurons: a calcium imaging study. J. Neurophysiol. 87, 1106–1117 (2002). This is a good example of the new level of analysis provided by calcium imaging and is very informative about processing in the antennal lobe.

    Article  Google Scholar 

  17. Laurent, G. & Davidowitz, H. Encoding of olfactory information with oscillating neural assemblies. Science 265, 1872–1875 (1994).

    Article  CAS  Google Scholar 

  18. Müller, D., Abel, R., Brandt, R., Zöckler, M. & Menzel, R. Differential parallel processing of olfactory information in the honeybee, Apis mellifera L. J. Comp. Physiol. A 188, 359–370 (2002). | PubMed

    Article  Google Scholar 

  19. Yasuyama, K., Meinertzhagen, I. A. & Schürmann, F. -W. Synaptic organization of the mushroom body calyx in Drosophila melanogaster. J. Comp. Neurol. 445, 211–226 (2002).

    Article  Google Scholar 

  20. Grünewald, B. Morphology of feedback neurons in the mushroom body of the honeybee, Apis mellifera. J. Comp. Neurol. 404, 114–126 (1999).

    Article  Google Scholar 

  21. Perez-Orive, J. et al. Oscillations and sparsening of odor representations in the mushroom bodies. Science 297, 359–365 (2002). Although this work is on locust, which has an atypical olfactory system, it systematically investigates for the first time the data transfer from projection neurons to Kenyon cells.

    Article  CAS  Google Scholar 

  22. Heisenberg, M. Genetic approach to learning and memory (mnemogenetics) in Drosophila melanogaster. Fortschritte Zool. 37, 3–45 (1989).

    Google Scholar 

  23. Menzel, R. Searching for the memory trace in a mini-brain, the honeybee. Learn. Mem. 8, 53–62 (2001). A recent summary of PER conditioning.

    Article  CAS  Google Scholar 

  24. Mauelshagen, J. Neural correlates of olfactory learning paradigms in an identified neuron in the honeybee brain. J. Neurophysiol. 69, 609–625 (1993).

    Article  CAS  Google Scholar 

  25. Heisenberg, M., Borst, A., Wagner, S. & Byers, D. Drosophila mushroom body mutants are deficient in olfactory learning. J. Neurogenet. 2, 1–30 (1985).

    Article  CAS  Google Scholar 

  26. de Belle, J. S. & Heisenberg, M. Associative odor learning in Drosophila abolished by chemical ablation of MBs. Science 263, 692–695 (1994).

    Article  CAS  Google Scholar 

  27. Connolly, J. B. et al. Associative learning disrupted by impaired Gs signaling in Drosophila mushroom bodies. Science 274, 2104–2107 (1996).

    Article  CAS  Google Scholar 

  28. Dudai, Y. Properties of learning and memory in Drosophila melanogaster. J. Comp. Physiol. 114, 69–89 (1977).

    Article  Google Scholar 

  29. Guo, A. & Götz, K. G. Association of visual objects and olfactory cues in Drosophila. Learn. Mem. 4, 192–204 (1997).

    Article  CAS  Google Scholar 

  30. Strauss, R., Renner, M. & Götz, K. G. Task-specific association of photoreceptor systems and steering parameters in Drosophila. J. Comp. Physiol. A 187, 617–632 (2001).

    Article  CAS  Google Scholar 

  31. Lechner, H. A. & Byrne, J. H. New perspectives on classical conditioning: a synthesis of Hebbian and non-Hebbian mechanisms. Neuron 20, 355–358 (1998).

    Article  CAS  Google Scholar 

  32. Koh, Y. H., Gramates, L. S. & Budnik, V. Drosophila larval neuromuscular junction: molecular components underlying synaptic plasticity. Microsc. Res. Tech. 49, 14–25 (2000).

    Article  CAS  Google Scholar 

  33. Levin, L. R. et al. The Drosophila learning and memory gene rutabaga encodes a Ca2+/calmodulin-responsive adenylyl cyclase. Cell 68, 479–489 (1992).

    Article  CAS  Google Scholar 

  34. Livingstone, M. S., Sziber, P. P. & Quinn, W. G. Loss of calcium/calmodulin responsiveness in adenylate cyclase of rutabaga, a Drosophila learning mutant. Cell 37, 205–215 (1984).

    Article  CAS  Google Scholar 

  35. Zars, T., Fischer, M., Schulz, R. & Heisenberg, M. Localization of a short-term memory in Drosophila. Science 288, 672–675 (2000). This paper and reference 39 emphasize the distinction between necessary and sufficient structures, heralding the power of reconstruction as opposed to dissection.

    Article  CAS  Google Scholar 

  36. Schwaerzel, M., Heisenberg, M. & Zars, T. Extinction antagonizes olfactory memory at the sub-cellular level. Neuron 35, 951–960 (2002). Localization of the memory trace of odours to Kenyon cell output synapses indicates that extinction occurs at these same synapses.

    Article  CAS  Google Scholar 

  37. Kitamoto, T. Conditional modification of behavior in Drosophila by targeted expression of a temperature-sensitive shibire allele in defined neurons. J. Neurobiol. 47, 81–92 (2001).

    Article  CAS  Google Scholar 

  38. Dubnau, J., Grady, L., Kitamoto, T. & Tully, T. Disruption of neurotransmission in Drosophila mushroom body blocks retrieval but not acquisition of memory. Nature 411, 476–480 (2001).

    Article  CAS  Google Scholar 

  39. McGuire, S. E., Le, P. T. & Davis, R. L. The role of mushroom body signaling in olfactory memory. Science 293, 1330–1334 (2001). References 38 and 39 show that output from the mushroom bodies is required for olfactory memory only during retrieval but not during acquisition.

    Article  CAS  Google Scholar 

  40. Grünewald, B. Physiological properties and response modulations of mushroom body feedback neurons during olfactory learning in the honeybee Apis mellifera. J. Comp. Physiol. A 185, 565–576 (1999).

    Article  Google Scholar 

  41. Bouton, M. E., Nelson, J. B. & Rosas, J. M. Stimulus generalization, context change, and forgetting. Psychol. Bull. 125, 171–186 (1999).

    Article  CAS  Google Scholar 

  42. Tully, T., Préat, T., Boynton, S. C. & DelVecchio, M. Genetic dissection of consolidated memory in Drosophila. Cell 79, 35–47 (1994).

    Article  CAS  Google Scholar 

  43. Feany, M. B. & Quinn, W. G. A neuropeptide gene defined by the Drosophila memory mutant amnesiac. Science 268, 869–873 (1995).

    Article  CAS  Google Scholar 

  44. Waddell, S., Armstrong, J. D., Kitamoto, T., Kaiser, K. & Quinn, W. G. The amnesiac gene product is expressed in two neurons in the Drosophila brain that are critical for memory. Cell 103, 805–813 (2000).

    Article  CAS  Google Scholar 

  45. Pascual, A. & Préat, T. Localization of long-term memory within the Drosophila mushroom bodies. Science 294, 1115–1117 (2001). The first link of long-term olfactory memory to the mushroom bodies.

    Article  CAS  Google Scholar 

  46. Huber, F. Untersuchungen über die Funktion des Zentralnervensystems und insbesondere des Gehirns bei der Fortbewegung und der Lauterzeugung der Grillen. Z. Vergl. Physiol. 44, 60–132 (1960).

    Article  Google Scholar 

  47. Martin, J. -R., Ernst, R. & Heisenberg, M. Mushroom bodies suppress locomotor activity in Drosophila melanogaster. Learn. Mem. 5, 179–191 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Mronz, M. & Strauss, R. Proper retreat from attractive but inaccessible landmarks requires the mushroom bodies. J. Neurogenet. (in the press).

  49. Heisenberg, M. & Wolf, R in Visual Motion and its Role in the Stabilization of Gaze (eds Miles, F. A. & Wallman, J.) 265–282 (Elsevier, Amsterdam, 1993).

    Google Scholar 

  50. Heisenberg, M., Wolf, R. & Brembs, B. Flexibility in a single behavioral variable of Drosophila. Learn. Mem. 8, 1–10 (2001). A short review of learning at the flight simulator.

    Article  CAS  Google Scholar 

  51. Wolf, R. & Heisenberg, M. Basic organization of operant behavior as revealed in Drosophila flight orientation. J. Comp. Physiol. A 169, 699–705 (1991).

    Article  CAS  Google Scholar 

  52. Xia, S. Z., Liu, L., Feng, C. H. & Guo, A. Memory consolidation in Drosophila operant visual learning. Learn. Mem. 4, 205–218 (1997).

    Article  CAS  Google Scholar 

  53. Wiener, J. M. Kontext-Generalisierung in Drosophila melanogaster. Thesis, Univ. Würzburg (2000).

  54. Liu, L., Wolf, R., Ernst, R. & Heisenberg, M. Context generalization in Drosophila visual learning requires the mushroom bodies. Nature 400, 753–756 (1999).

    Article  CAS  Google Scholar 

  55. Tang, S. & Guo, A. Choice behavior of Drosophila facing contradictory visual cues. Science 294, 1543–1547 (2001). A fascinating, new non-olfactory function of the mushroom bodies in 'decisions'.

    Article  CAS  Google Scholar 

  56. Mizunami, M., Weibrecht, J. M. & Strausfeld, N. J. Mushroom bodies of the cockroach: their participation in place memory. J. Comp. Neurol. 402, 520–537 (1998).

    Article  CAS  Google Scholar 

  57. Mizunami, M., Okada, R., Li, Y. -S. & Strausfeld, N. J. Mushroom bodies of the cockroach: activity and identities of neurons recorded in freely moving animals. J. Comp. Neurol. 402, 501–519 (1998).

    Article  CAS  Google Scholar 

  58. Hammer, M. An identified neuron mediates the unconditioned stimulus in associative olfactory learning in honeybees. Nature 366, 59–63 (1993).

    Article  CAS  Google Scholar 

  59. Kreissl, S., Eichmüller, S., Bicker, G., Rapus, J. & Eckert, M. Octopamine-like immunoreactivity in the brain and suboesophageal ganglion of the honeybee. J. Comp. Neurol. 348, 583–595 (1994).

    Article  CAS  Google Scholar 

  60. Hammer, M. & Menzel, R. Multiple sites of associative odor learning as revealed by local brain microinjections of octopamine in honeybees. Learn. Mem. 5, 146–156 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Han, P. L., Levin, L. R., Reed, R. R. & Davis, R. L. Preferential expression of the Drosophila rutabaga gene in mushroom bodies, neural centers for learning in insects. Neuron 9, 619–627 (1992).

    Article  CAS  Google Scholar 

  62. Heisenberg, M. & Böhl, K. Isolation of anatomical brain mutants of Drosophila by histological means. Z. Naturforschung C 34, 143–147 (1979).

    Article  Google Scholar 

  63. Brand, A. & Perrimon, N. Targeted gene expression as a means of altering cell fate and generating dominant phenotypes. Development 118, 401–415 (1993).

    CAS  Google Scholar 

  64. Crittenden, J. R., Skoulakis, E. M. C., Han, K. -A., Kalderon, D. & Davis, R. L. Tripartite mushroom body architecture revealed by antigenic markers. Learn. Mem. 5, 38–51 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. DeZazzo, J. & Tully, T. Dissection of memory formation: from behavioral pharmacology to molecular genetics. Trends Neurosci. 18, 212–218 (1995).

    Article  CAS  Google Scholar 

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Acknowledgements

I am indebted to B. Gerber for a discussion of the manuscript, to N. Strausfeld and T. Préat for sharing unpublished data, and to the German Science Foundation and the Human Frontiers Science Program for financial support.

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Consistency in response to odourant molecules across different concentrations.

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Heisenberg, M. Mushroom body memoir: from maps to models. Nat Rev Neurosci 4, 266–275 (2003). https://doi.org/10.1038/nrn1074

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