Journal of Computational Neuroscience

, Volume 24, Issue 2, pp 207–221 | Cite as

Dendritic action potentials connect distributed dendrodendritic microcircuits

  • M. Migliore
  • Gordon M. Shepherd


Lateral inhibition of cells surrounding an excited area is a key property of sensory systems, sharpening the preferential tuning of individual cells in the presence of closely related input signals. In the olfactory pathway, a dendrodendritic synaptic microcircuit between mitral and granule cells in the olfactory bulb has been proposed to mediate this type of interaction through granule cell inhibition of surrounding mitral cells. However, it is becoming evident that odor inputs result in broad activation of the olfactory bulb with interactions that go beyond neighboring cells. Using a realistic modeling approach we show how backpropagating action potentials in the long lateral dendrites of mitral cells, together with granule cell actions on mitral cells within narrow columns forming glomerular units, can provide a mechanism to activate strong local inhibition between arbitrarily distant mitral cells. The simulations predict a new role for the dendrodendritic synapses in the multicolumnar organization of the granule cells. This new paradigm gives insight into the functional significance of the patterns of connectivity revealed by recent viral tracing studies. Together they suggest a functional wiring of the olfactory bulb that could greatly expand the computational roles of the mitral–granule cell network.


Olfactory processing Modeling Mitral cells Granule cells 



We are grateful for the support by the National Institutes of Health Grant DC00086 and DC003918, and the Human Brain Project (National Institute of Deafness and Other Communication Disorders, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, National Institute on Aging, and the National Science Foundation). We thank W. Chen, C. Greer, D. Johnston, J. Midtgaard, W. Rall, and D. Willhite for the valuable suggestions and discussions.


  1. Abraham, N. M., Spors, H., Carleton, A., Margrie, T. W., Kuner, T., & Schaefer, A. T. (2004). Maintaining accuracy at the expense of speed: Stimulus similarity defines odor discrimination time in mice. Neuron, 44, 865–876.PubMedGoogle Scholar
  2. Bischofberger, J., & Jonas, P. (1997). Action potential propagation into the presynaptic dendrites of rat mitral cells. Journal of Physiology, 504, 359–365.PubMedCrossRefGoogle Scholar
  3. Cang, J., & Isaacson, J. S. (2003). In vivo whole-cell recording of odor-evoked synaptic transmission in the rat olfactory bulb. Journal of Neuroscience, 23, 4108–4116.PubMedGoogle Scholar
  4. Chen, W. R., Midtgaard, J., & Shepherd, G. M. (1997). Forward and backward propagation of dendritic impulses and their synaptic control in mitral cells. Science, 278, 463–467.PubMedCrossRefGoogle Scholar
  5. Chen, W. R., Shen, G. Y., Shepherd, G. M., Hines, M. L., & Midtgaard, J. (2002). Multiple modes of action potential initiation and propagation in mitral cell primary dendrite. Journal of Neurophysiology, 88, 2755–2764.PubMedCrossRefGoogle Scholar
  6. Chen, W. R., Xiong, W., & Shepherd, G. M. (2000). Analysis of relations between NMDA receptors and GABA release at olfactory bulb reciprocal synapses. Neuron, 25, 625–633.PubMedCrossRefGoogle Scholar
  7. Christie, J. M., & Westbrook, G. L. (2003). Regulation of backpropagating action potentials in mitral cell lateral dendrites by A-type potassium currents. Journal of Neurophysiology, 89, 2466–2472.PubMedCrossRefGoogle Scholar
  8. Cleland, T. A., & Linster, C. (2005). Computation in the olfactory system. Chemical Senses, 30, 801–813.PubMedCrossRefGoogle Scholar
  9. Cleland, T. A., & Sethupathy, P. (2006). Non-topographical contrast enhancement in the olfactory bulb. BMC Neuroscience, 7, 7.PubMedCrossRefGoogle Scholar
  10. Davison, A. P., Feng, J., & Brown, D. (2003). Dendrodendritic inhibition and simulated odor responses in a detailed olfactory bulb network model. Journal of Neurophysiology, 90, 1921–1935.PubMedCrossRefGoogle Scholar
  11. Debarbieux, F., Audinat, E., & Charpak, S. (2003). Action potential propagation in dendrites of rat mitral cells in vivo. Journal of Neuroscience, 23, 5553–5560.PubMedGoogle Scholar
  12. Destexhe, A., Mainen, Z. F., & Sejnowski, T. J. (1994). An efficient method for computing synaptic conductances based on a kinetic model of receptor binding. Neural Computation, 6, 10–14.CrossRefGoogle Scholar
  13. Egger, V., Svoboda, K., & Mainen, Z. F. (2003). Mechanisms of lateral inhibition in the olfactory bulb: Efficiency and modulation of spike-evoked calcium influx into granule cells. Journal of Neuroscience, 23, 7551–7558.PubMedGoogle Scholar
  14. Egger, V., Svoboda, K., & Mainen, Z. F. (2005). Dendrodendritic synaptic signals in olfactory bulb granule cells: Local spine boost and global low-threshold spike. Journal of Neuroscience, 25, 3521–3530.PubMedCrossRefGoogle Scholar
  15. Egger, V., & Urban, N. N. (2006). Dynamic connectivity in the mitral cell–granule cell microcircuit. Seminars in Cell & Developmental Biology, 17, 424–432.CrossRefGoogle Scholar
  16. Hines, M., & Carnevale, T. (1997). The NEURON simulation environment. Neural Computation, 9, 178–1209.CrossRefGoogle Scholar
  17. Isaacson, J. S. (2001). Mechanisms governing dendritic gamma-aminobutyric acid (GABA) release in the rat olfactory bulb. Proceedings of the National Academy of Sciences of the United States of America, 98, 337–342.PubMedCrossRefGoogle Scholar
  18. Jahr, C. E., & Stevens, C. F. (1990a). A quantitative description of NMDA receptor-channel kinetic behavior. Journal of Neuroscience, 10, 1830–1837.PubMedGoogle Scholar
  19. Jahr, C. E., & Stevens, C. F. (1990b). Voltage dependence of NMDA-activated macroscopic conductances predicted by single-channel kinetics. Journal of Neuroscience, 10, 3178–3182.PubMedGoogle Scholar
  20. Kuffler, S. W. (1953). Discharge patterns and functional organization of mammalian retina. Journal of Neurophysiology, 16, 37–68.PubMedGoogle Scholar
  21. Leon, M., & Johnson, B. A. (2003). Olfactory coding in the mammalian olfactory bulb. Brain Research Review, 42, 23–32.CrossRefGoogle Scholar
  22. Linster, C., & Hasselmo, M. (1997). Modulation of inhibition in a model of olfactory bulb reduces overlap in the neural representation of olfactory stimuli. Behavioural Brain Research, 84, 117–127.PubMedCrossRefGoogle Scholar
  23. Lowe, G. (2002). Inhibition of backpropagating action potentials in mitral cell secondary dendrites. Journal of Neurophysiology, 88, 64–85.PubMedGoogle Scholar
  24. Margrie, T. W., Sakmann, B., & Urban, N. N. (2001). Action potential propagation in mitral cell lateral dendrites is decremental and controls recurrent and lateral inhibition in the mammalian olfactory bulb. Proceedings of the National Academy of Sciences of the United States of America, 98, 319–324.PubMedCrossRefGoogle Scholar
  25. Migliore, M., Hines, M. L., & Shepherd, G. M. (2005). The role of distal dendritic gap junctions in synchronization of mitral cell axonal output. Journal of Computational Neuroscience, 18, 151–161.PubMedCrossRefGoogle Scholar
  26. Mori, K., Nowycky, M. C., & Shepherd, G. M. (1981). Electrophysiological analysis of mitral cells in the isolated turtle olfactory bulb. Journal of Physiology, 314, 281–294.PubMedGoogle Scholar
  27. Mori, K., Takahashi, Y. K., Igarashi, K. M., & Yamaguchi, M. (2006). Maps of odorant molecular features in the Mammalian olfactory bulb. Physiological Reviews, 86, 409–433.PubMedCrossRefGoogle Scholar
  28. Mombaerts, P. (1996). Targeting olfaction. Current Opinion in Neurobiology, 6, 481–486.PubMedCrossRefGoogle Scholar
  29. Pinato, G., & Midtgaard, J. (2004). Dendritic sodium spikelets and low-threshold calcium spikes in turtle olfactory bulb granule cells. Journal of Neurophysiology, 93, 1285–1294.PubMedCrossRefGoogle Scholar
  30. Rall, W., & Shepherd, G. M. (1968). Theoretical reconstruction of field potentials and dendrodendritic synaptic interactions in olfactory bulb. Journal of Neurophysiology, 31, 884–915.PubMedGoogle Scholar
  31. Rall, W., Shepherd, G. M., Reese, T. S., & Brightman, M. W. (1966). Dendrodendritic synaptic pathway for inhibition in the olfactory bulb. Experimental Neurology, 14, 44–56.PubMedCrossRefGoogle Scholar
  32. Ressler, K. J., Sullivan, S. L., & Buck, L. B. (1994). Information coding in the olfactory system: Evidence for a stereotyped and highly organized epitope map in the olfactory bulb. Cell, 79, 1245–1255.PubMedCrossRefGoogle Scholar
  33. Schoppa, N. E., Kinzie, J. M., Sahara, Y., Segerson, T. P., & Westbrook, G. L. (1998). Dendrodendritic inhibition in the olfactory bulb is driven by NMDA receptors. Journal of Neuroscience, 18, 6790–6802.PubMedGoogle Scholar
  34. Schoppa, N. E., & Westbrook, G. L. (1999). Regulation of synaptic timing in the olfactory bulb by an A-type potassium current. Nature Neuroscience, 2, 1106–1113.PubMedCrossRefGoogle Scholar
  35. Shepherd, G. M., & Brayton, R. K. (1979). Computer simulation of a dendrodendritic synaptic circuit for self- and lateral-inhibition in the olfactory bulb. Brain Research, 175, 377–382.PubMedCrossRefGoogle Scholar
  36. Shepherd, G. M., & Greer, C. A. (1998). Olfactory bulb. In G. M. Shepherd (Ed.), The synaptic organization of the brain. New York: Oxford University Press, p. 170.Google Scholar
  37. Uchida, N., & Mainen, Z. F. (2003). Speed and accuracy of olfactory discrimination in the rat. Nature Neuroscience, 6, 1224–1229.PubMedCrossRefGoogle Scholar
  38. Urban, N. N., & Sakmann, B. (2002). Reciprocal intraglomerular excitation and intra- and interglomerular lateral inhibition between mouse olfactory bulb mitral cells. Journal of Physiology, 542, 355–367.PubMedCrossRefGoogle Scholar
  39. Vassar, R., Chao, S. K., Sitcheran, R., Nunez, J. M., Vosshall, L. B., & Axel, R. (1994). Topographic organization of sensory projections to the olfactory bulb. Cell, 79, 981–991.PubMedCrossRefGoogle Scholar
  40. Wellis, D. P., & Kauer, J. S. (1994). GABAergic and glutamatergic synaptic input to identified granule cells in salamander olfactory bulb. Journal of Physiology, 475, 419–430.PubMedGoogle Scholar
  41. Willhite, D. C., Nguyen, K. T., Masurkar, A. V., Greer, C. A., Shepherd, G. M., & Chen, W. R. (2006). Viral tracing identifies distributed columnar organization in the olfactory bulb. Proceedings of the National Academy of Sciences of the United States of America, 103, 12592–12597.PubMedCrossRefGoogle Scholar
  42. Woolf, T. B., Shepherd, G. M., & Greer, C. A. (1991). Local information processing in dendritic trees: Subsets of spines in granule cells of the mammalian olfactory bulb. Journal of Neuroscience, 11, 1837–1854.PubMedGoogle Scholar
  43. Xiong, W., & Chen, W. R. (2002). Dynamic gating of spike propagation in the mitral cell lateral dendrites. Neuron, 34, 115–126.PubMedCrossRefGoogle Scholar
  44. Xu, F. Q., Liu, N., Kida, I., Rothman, D. L., Hyder, F., & Shepherd, G. M. (2003). Odor maps of aldehydes and esters revealed by fMRI in the glomerular layer of the mouse olfactory bulb. Proceedings of the National Academy of Sciences of the United States of America, 100, 11029–11034.PubMedCrossRefGoogle Scholar
  45. Yokoi, M., Mori, K., & Nakanishi, S. (1995). Refinement of odor molecule tuning by dendrodendritic synaptic inhibition in the olfactory bulb. Proceedings of the National Academy of Sciences of the United States of America, 92, 3371–3375.PubMedCrossRefGoogle Scholar
  46. Zelles, Y., Boyd, J. D., Hardy, A. B., & Delaney, K. R. (2006). Branch-specific Ca2+ influx from Na+-dependent dendritic spikes in olfactory granule cells. Journal of Neuroscience, 26, 30–40.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.Department of NeurobiologyYale University School of MedicineNew HavenUSA
  2. 2.Institute of BiophysicsNational Research CouncilPalermoItaly

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