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Conditional modulation of spike-timing-dependent plasticity for olfactory learning

A Corrigendum to this article was published on 04 July 2012


Mushroom bodies are a well-known site for associative learning in insects. Yet the precise mechanisms that underlie plasticity there and ensure their specificity remain elusive. In locusts, the synapses between the intrinsic mushroom body neurons and their postsynaptic targets obey a Hebbian spike-timing-dependent plasticity (STDP) rule. Although this property homeostatically regulates the timing of mushroom body output, its potential role in associative learning is unknown. Here we show in vivo that pre–post pairing causing STDP can, when followed by the local delivery of a reinforcement-mediating neuromodulator, specify the synapses that will undergo an associative change. At these synapses, and there only, the change is a transformation of the STDP rule itself. These results illustrate the multiple actions of STDP, including a role in associative learning, despite potential temporal dissociation between the pairings that specify synaptic modification and the delivery of reinforcement-mediating neuromodulator signals.

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Figure 1: Beta-lobe neurons are promiscuous.
Figure 2: Saturation of activity caused by STDP can be counteracted by lateral inhibition.
Figure 3: OCT changes the STDP rule.
Figure 4: Odour-specific decrease of mushroom body output by OCT.


  1. McGuire, S. E., Le, P. T. & Davis, R. L. The role of Drosophila mushroom body signaling in olfactory memory. Science 293, 1330–1333 (2001)

    Article  ADS  CAS  PubMed  Google Scholar 

  2. Tully, J. B. C. T. in Drosophila: A Practical Approach (ed. Roberts, D. B. ) 265–317 (Oxford Univ. Press, 1998)

    Google Scholar 

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

    Article  ADS  CAS  PubMed  Google Scholar 

  4. Tully, T. & Quinn, W. G. Classical conditioning and retention in normal and mutant Drosophila melanogaster . J. Comp. Physiol. A 157, 263–277 (1985)

    Article  CAS  PubMed  Google Scholar 

  5. 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  PubMed  Google Scholar 

  6. Quinn, W. G., Harris, W. A. & Benzer, S. Conditioned behavior in Drosophila melanogaster . Proc. Natl Acad. Sci. USA 71, 708–712 (1974)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  7. Keene, A. C. & Waddell, S. Drosophila olfactory memory: single genes to complex neural circuits. Nature Rev. Neurosci. 8, 341–354 (2007)

    Article  CAS  Google Scholar 

  8. Akalal, D. B. et al. Roles for Drosophila mushroom body neurons in olfactory learning and memory. Learn. Mem. 13, 659–668 (2006)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Davis, R. L. Olfactory memory formation in Drosophila: from molecular to systems neuroscience. Annu. Rev. Neurosci. 28, 275–302 (2005)

    Article  CAS  PubMed  Google Scholar 

  10. Gerber, B., Tanimoto, H. & Heisenberg, M. An engram found? Evaluating the evidence from fruit flies. Curr. Opin. Neurobiol. 14, 737–744 (2004)

    Article  CAS  PubMed  Google Scholar 

  11. Heisenberg, M. Mushroom body memoir: from maps to models. Nature Rev. Neurosci. 4, 266–275 (2003)

    Article  CAS  Google Scholar 

  12. Perez-Orive, J. et al. Oscillations and sparsening of odor representations in the mushroom body. Science 297, 359–365 (2002)

    Article  ADS  CAS  PubMed  Google Scholar 

  13. Turner, G. C., Bazhenov, M. & Laurent, G. Olfactory representations by Drosophila mushroom body neurons. J. Neurophysiol. 99, 734–746 (2008)

    Article  PubMed  Google Scholar 

  14. Ito, I., Ong, R. C.-Y., Raman, B. & Stopfer, M. Sparse odor representation and olfactory learning. Nature Neurosci. 11, 1177–1184 (2008)

    Article  CAS  PubMed  Google Scholar 

  15. Kanerva, P. Sparse Distributed Memory (MIT Press, 1988)

    MATH  Google Scholar 

  16. Papadopoulou, M., Cassenaer, S., Nowotny, T. & Laurent, G. Normalization for sparse encoding of odors by a wide-field interneuron. Science 332, 721–725 (2011)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  17. Cassenaer, S. & Laurent, G. Hebbian STDP in mushroom bodies facilitates the synchronous flow of olfactory information in locusts. Nature 448, 709–713 (2007)

    Article  ADS  CAS  PubMed  Google Scholar 

  18. Markram, H., Lübke, J., Frotscher, M. & Sakmann, B. Regulation of synaptic efficacy by coincidence of postsynaptic APs and EPSPs. Science 275, 213–215 (1997)

    Article  CAS  PubMed  Google Scholar 

  19. Bi, G. Q. & Poo, M. M. Synaptic modifications in cultured hippocampal neurons: dependence on spike timing, synaptic strength, and postsynaptic cell type. J. Neurosci. 18, 10464–10472 (1998)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Abbott, L. F. & Nelson, S. B. Synaptic plasticity: taming the beast. Nature Neurosci. 3, 1178–1183 (2000)

    Article  CAS  PubMed  Google Scholar 

  21. Meeks, J. P. & Holy, T. E. Pavlov’s moth: olfactory learning and spike-timing-dependent plasticity. Nature Neurosci. 11, 1126–1127 (2008)

    Article  CAS  PubMed  Google Scholar 

  22. Pawlak, V. et al. Timing is not everything: neuromodulation opens the STDP gate. Front. Syn. Neurosci. 2, 146 (2010)

    Article  Google Scholar 

  23. Izhikevich, E. M. Solving the distal reward problem through linkage of STDP and dopamine signaling. Cereb. Cortex 17, 2443–2452 (2007)

    Article  PubMed  Google Scholar 

  24. Gütig, R., Aharonov, R., Rotter, S. & Sompolinsky, H. Learning input correlations through nonlinear temporally asymmetric Hebbian plasticity. J. Neurosci. 23, 3697–3714 (2003)

    Article  PubMed  PubMed Central  Google Scholar 

  25. Huerta, R., Nowotny, T., García-Sanchez, M., Abarbanel, H. D. I. & Rabinovich, M. I. Learning classification in the olfactory system of insects. Neural Comput. 16, 1601–1640 (2004)

    Article  PubMed  Google Scholar 

  26. Masquelier, T. & Thorpe, S. J. Unsupervised learning of visual features through spike timing dependent plasticity. PLoS Comput. Biol. 3, e31 (2007)

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  27. Waddell, S. & Quinn, W. G. Learning how a fruit fly forgets. Science 293, 1271–1272 (2001)

    Article  CAS  PubMed  Google Scholar 

  28. Isabel, G., Pascual, A. & Preat, T. Exclusive consolidated memory phases in Drosophila . Science 304, 1024–1027 (2004)

    Article  ADS  CAS  PubMed  Google Scholar 

  29. Gervasi, N., Tchénio, P. & Preat, T. PKA dynamics in a Drosophila learning center: coincidence detection by rutabaga adenylyl cyclase and spatial regulation by dunce phosphodiesterase. Neuron 65, 516–529 (2010)

    Article  CAS  PubMed  Google Scholar 

  30. Wang, Y., Mamiya, A., Chiang, A. S. & Zhong, Y. Imaging of an early memory trace in the Drosophila mushroom body. J. Neurosci. 28, 4368–4376 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Claridge-Chang, A. et al. Writing memories with light-addressable reinforcement circuitry. Cell 139, 405–415 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Kim, Y. C., Lee, H. G. & Han, K. A. D1 dopamine receptor dDA1 is required in the mushroom body neurons for aversive and appetitive learning in Drosophila . J. Neurosci. 27, 7640–7647 (2007)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Riemensperger, T., Voller, T., Stock, P., Buchner, E. & Fiala, A. Punishment prediction by dopaminergic neurons in Drosophila . Curr. Biol. 15, 1953–1960 (2005)

    Article  CAS  PubMed  Google Scholar 

  34. Schwaerzel, M. et al. Dopamine and octopamine differentiate between aversive and appetitive olfactory memories in Drosophila . J. Neurosci. 23, 10495–10502 (2003)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Mizunami, M. & Matsumoto, Y. Roles of aminergic neurons in formation and recall of associative memory in crickets. Front. Behav. Neurosci. 4, 172 (2010)

    PubMed  PubMed Central  Google Scholar 

  36. Braunig, P. Suboesophageal DUM neurons innervate the principal neuropiles of the locust brain. Phil. Trans. R. Soc. Lond. B 332, 221–240 (1991)

    Article  ADS  Google Scholar 

  37. Wendt, B. & Homberg, U. Immunocytochemistry of dopamine in the brain of the locust Schistocerca gregaria . J. Comp. Neurol. 321, 387–403 (1992)

    Article  CAS  PubMed  Google Scholar 

  38. Laurent, G. & Naraghi, M. Odorant-induced oscillations in the mushroom bodies of the locust. J. Neurosci. 14, 2993–3004 (1994)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  ADS  CAS  PubMed  Google Scholar 

  40. Gütig, R. & Sompolinsky, H. The tempotron: a neuron that learns spike timing-based decisions. Nature Neurosci. 9, 420–428 (2006)

    Article  PubMed  Google Scholar 

  41. Huerta, R. & Nowotny, T. Fast and robust learning by reinforcement signals: explorations in the insect brain. Neural Comput. 21, 2123–2151 (2009)

    Article  PubMed  Google Scholar 

  42. Seol, G. H. et al. Neuromodulators control the polarity of spike-timing- dependent synaptic plasticity. Neuron 55, 919–929 (2007)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Shen, W., Flajolet, M., Greengard, P. & Surmeier, D. J. Dichotomous dopaminergic control of striatal synaptic plasticity. Science 321, 848–851 (2008)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  44. Izhikevich, E. M. Simple model of spiking neurons. IEEE Trans. Neural Netw. 14, 1569–1572 (2003)

    Article  CAS  PubMed  Google Scholar 

  45. Mazor, O. & Laurent, G. Transient dynamics versus fixed points in odor representations by locust antennal lobe projection neurons. Neuron 48, 661–673 (2005)

    Article  CAS  PubMed  Google Scholar 

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This work was funded by the Lawrence Hanson Chair at Caltech, the National Institutes on Deafness and other Communication Disorders, Caltech's Broad Fellows Program, the Office of Naval Research (grants N00014-07-1-0741 and N00014-10-1-0735) and the Max Planck Society. We are grateful to L.-P. Mok for help with locust dissections and to E. Schuman, A. Siapas, E. Lubenov, M. Papadopoulou and members of the Laurent lab for comments on the manuscript.

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S.C. and G.L. designed the experiments and simulations, discussed the results and wrote the paper. S.C. carried out the experiments and simulations.

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Correspondence to Stijn Cassenaer or Gilles Laurent.

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The authors declare no competing financial interests.

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Cassenaer, S., Laurent, G. Conditional modulation of spike-timing-dependent plasticity for olfactory learning. Nature 482, 47–52 (2012).

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