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Journal of Computational Neuroscience

, Volume 44, Issue 1, pp 1–24 | Cite as

New class of reduced computationally efficient neuronal models for large-scale simulations of brain dynamics

  • Maxim Komarov
  • Giri Krishnan
  • Sylvain Chauvette
  • Nikolai Rulkov
  • Igor Timofeev
  • Maxim Bazhenov
Article

Abstract

During slow-wave sleep, brain electrical activity is dominated by the slow (< 1 Hz) electroencephalogram (EEG) oscillations characterized by the periodic transitions between active (or Up) and silent (or Down) states in the membrane voltage of the cortical and thalamic neurons. Sleep slow oscillation is believed to play critical role in consolidation of recent memories. Past computational studies, based on the Hodgkin-Huxley type neuronal models, revealed possible intracellular and network mechanisms of the neuronal activity during sleep, however, they failed to explore the large-scale cortical network dynamics depending on collective behavior in the large populations of neurons. In this new study, we developed a novel class of reduced discrete time spiking neuron models for large-scale network simulations of wake and sleep dynamics. In addition to the spiking mechanism, the new model implemented nonlinearities capturing effects of the leak current, the Ca2+ dependent K+ current and the persistent Na+ current that were found to be critical for transitions between Up and Down states of the slow oscillation. We applied the new model to study large-scale two-dimensional cortical network activity during slow-wave sleep. Our study explained traveling wave dynamics and characteristic synchronization properties of transitions between Up and Down states of the slow oscillation as observed in vivo in recordings from cats. We further predict a critical role of synaptic noise and slow adaptive currents for spike sequence replay as found during sleep related memory consolidation.

Keywords

Slow-wave sleep oscillations Large-scale simulations Up and down states 

Notes

Acknowledgements

This work was supported by grants from ONR (MURI: N000141310672), NIH (MH099645) and Canadian Institutes of Health Research (MOP-136969, MOP-136967). MK and NR also appreciate partial support from ONR grant N00014-16-1-2252.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Achermann, P., & Borbely, A. A. (1997). Low-frequency (<1 Hz) oscillations in the human sleep electroencephalogram. Neuroscience, 81(1), 213–222.Google Scholar
  2. Aeschbacj, D., Borbely, A.A. (1993). All-night dynamics of the human sleep EEG. Journal of Sleep Research, 2(2), 70–81.Google Scholar
  3. Ali, M. M., Sellers, K. K., & Fröhlich, F. (2013). Transcranial alternating current stimulation modulates large-scale cortical network activity by network resonance. The Journal of Neuroscience, 33(27), 11262–11275.  https://doi.org/10.1523/JNEUROSCI.5867-12.2013 PubMed.CrossRefPubMedGoogle Scholar
  4. Anderson, C. R., & Stevens, C. F. (1973). Voltage clamp analysis of acetylcholine produced ebd-plate current fluctuations at frog neuromoscular junction. Journal of Physiology, 235, 655–691 PubMed.CrossRefPubMedPubMedCentralGoogle Scholar
  5. Bazhenov, M., Timofeev, I., Steriade, M., & Sejnowski, T. J. (2002). Model of thalamocortical slow-wave sleep oscillations and transitions to activated States. The Journal of neuroscience : the official journal of the Society for Neuroscience, 22(19), 8691–8704 PubMed.Google Scholar
  6. Bazhenov, M., Rulkov, N. F., & Timofeev, I. (2008). Effect of synaptic connectivity on long-range synchronization of fast cortical oscillations. Journal of neurophysiology, 100(3), 1562–1575.  https://doi.org/10.1152/jn.90613.2008 PubMed.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Borbely, A. A., Baumann, F., Brandeis, D., Strauch, I., & Lehmann, D. (1981). Sleep deprivation: effect on sleep stages and EEG power density in man. Electroencephalography and Clinical Neurophysiology, 51(5), 483–495 Epub 1981/05/01. PubMed.CrossRefPubMedGoogle Scholar
  8. Brette, R., & Gerstner, W. (2005). Adaptive exponential integrate-and-fire model as an effective description of neuronal activity. Journal of neurophysiology, 94(5), 3637–3642.  https://doi.org/10.1152/jn.00686.2005 PubMed.CrossRefPubMedGoogle Scholar
  9. Buhl, E. H., Tams, G., Szilgyi, T., Stricker, C., Paulsen, O., & Somogyi, P. (1997). Effect, number and location of synapses made by single pyramidal cells onto aspiny interneurones of cat visual cortex. The Journal of physiology, 500(Pt 3), 689–713 PubMed.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Casti, A.R.R., Omurtag, A., Sornborger, A., Kaplan, E., Knight, B., Victor, J., et al. (2002). A population study of integrate-and-fire-or-burst neurons. Neural computation, 14(5), 957–986.  https://doi.org/10.1162/089976602753633349 PubMed.CrossRefPubMedGoogle Scholar
  11. Chauvette, S., Volgushev, M., & Timofeev, I. (2010). Origin of Active States in Local Neocortical Networks during Slow Sleep Oscillation. Cerebral Cortex, p., 2660–2674.Google Scholar
  12. Chauvette, S., Crochet, S., Volgushev, M., & Timofeev, I. (2011). Properties of Slow Oscillation during Slow-Wave Sleep and Anesthesia in Cats. The Journal of Neuroscience., 31(42), 14998–15008.  https://doi.org/10.1523/JNEUROSCI.2339-11.2011.CrossRefPubMedPubMedCentralGoogle Scholar
  13. Chen, J.-Y., Chauvette, S., Skorheim, S., Timofeev, I., & Bazhenov, M. (2012). Interneuron-mediated inhibition synchronizes neuronal activity during slow oscillation. The Journal of physiology, 590(Pt 16), 3987–4010.  https://doi.org/10.1113/jphysiol.2012.227462 PubMed.CrossRefPubMedPubMedCentralGoogle Scholar
  14. Compte, A., Sanchez-Vives, M. V., McCormick, D. A., & Wang, X.-J. (2003). Cellular and network mechanisms of slow oscillatory activity (<1 Hz) and wave propagations in a cortical network model. Journal of Neurophysiology, 89(5), 2707–2725.CrossRefPubMedGoogle Scholar
  15. Contreras, D., & Steriade, M. (1995). Cellular basis of EEG slow rhythms: a study of dynamic corticothalamic relationships. The Journal of neuroscience, 15(1), 604–622 PubMed.PubMedGoogle Scholar
  16. Contreras, D., Timofeev, I., & Steriade, M. (1996). Mechanisms of long-lasting hyperpolarizations underlying slow sleep oscillations in cat corticothalamic networks. Journal of Physiology, 251–264.Google Scholar
  17. Contreras, D., Destexhe, A., Sejnowski, T., & Steriade, M. (1997). Spatiotemporal patterns of spindle oscillations in cortex and thalamus. Journal of Neuroscience, 1179–1196.Google Scholar
  18. Crook, S. M., Ermentrout, G. B., Vanier, M. C., & Bower, J. M. (1997). The role of axonal delay in the synchronization of networks of coupled cortical oscillators. Journal of Computational Neuroscience, 4(2), 161–172.  https://doi.org/10.1023/A:1008843412952 PubMed.CrossRefPubMedGoogle Scholar
  19. Destexhe, A. (2009). Self-sustained asynchronous irregular states and Up–Down states in thalamic, cortical and thalamocortical networks of nonlinear integrate-and-fire neurons. Journal of Computational Neuroscience, 27(3), 493–506.  https://doi.org/10.1007/s10827-009-0164-4 PubMed.CrossRefPubMedGoogle Scholar
  20. Destexhe, A., & Pare, D. (1999). Impact of Network Activity on the Integrative Properties of Neocortical Pyramidal Neurons In Vivo. Journal of Neurophysiology, 81, 1531–1547 PubMed.CrossRefPubMedGoogle Scholar
  21. Destexhe, A., Contreras, D., Sejnowski, T. J., & Steriade, M. (1994). A Model of Spindle Rhythmicity in the Isolated Thalamic Reticular Nucleus. Journal of neurophysiology, 72(2), 803–818 PubMed.CrossRefPubMedGoogle Scholar
  22. Diekelmann, S., & Born, J. (2010). The memory function of sleep. Nature reviews Neuroscience, 11(2), 114–126.  https://doi.org/10.1038/nrn2762 PubMed.PubMedGoogle Scholar
  23. Esser, S. K., Hill, S. L., & Tononi, G. (2007). Sleep homeostasis and cortical synchronization: I. Modeling the effects of synaptic strength on sleep slow waves. Sleep, 30(12), 1617–1630 PubMed PMID: 18246972; PubMed Central PMCID: PMCPMC2276134.CrossRefPubMedPubMedCentralGoogle Scholar
  24. Fleidervish, I. A., Friedman, A., & Gutnick, M. J. (1996). Slow inactivation of Na current and slow cumulative spike adaptation in mouse and guinea-pig neocortical neurones in slices. Journal of Physiology, 493(1), 83–97 PubMed.CrossRefPubMedPubMedCentralGoogle Scholar
  25. Gil, Z., Connors, B. W., & Amitai, Y. (1997). Differential regulation of neocortical synapses by neuromodulators and activity. Neuron, 679-86.Google Scholar
  26. Guan, D., Lee, J. C. F., Tkatch, T., Surmeier, D. J., Armstrong, W. E., & Foehring, R. C. (2006). Expression and biophysical properties of Kv1 channels in supragranular neocortical pyramidal neurones. The Journal of physiology, 571(Pt 2), 371–389.  https://doi.org/10.1113/jphysiol.2005.097006 PubMed.CrossRefPubMedGoogle Scholar
  27. Guan, D., Lee, J. C. F., Higgs, M. H., Spain, W. J., & Foehring, R. C. (2007). Functional roles of Kv1 channels in neocortical pyramidal neurons. Journal of neurophysiology, 97(3), 1931–1940.  https://doi.org/10.1152/jn.00933.2006 PubMed.CrossRefPubMedGoogle Scholar
  28. Gutkin, B. S., & Ermentrout, G. B. (1998). Dynamics of membrane excitability determine interspike interval variability: a link between spike generation mechanisms and cortical spike train statistics. Neural computation, 10(Cv)), 1047–1065.  https://doi.org/10.1162/089976698300017331 PubMed.CrossRefPubMedGoogle Scholar
  29. Hill, S., & Tononi, G. (2005). Modeling sleep and wakefulness in the thalamocortical system. Journal of Neurophysiology, 93(3), 1671–1698 PubMed.CrossRefPubMedGoogle Scholar
  30. Hodgkin, A., & Huxley, A. (1952). A quantitative description of membrane current and its application to conduction and excitation in nerve. Journal Physiol, 117, 500–544.  https://doi.org/10.1016/S0092-8240(05)80004-7 PubMed.CrossRefGoogle Scholar
  31. Hoppensteadt, F. C., & Izhikevich, E. M. (1996). Biological Cybernetics. Biological cybernetics, 127(2), 117–127 PubMed.CrossRefGoogle Scholar
  32. Izhikevich, E. M. (2004). Which model to use for cortical spiking neurons? IEEE Transactions on Neural Networks, 15(5), 1063–1070.  https://doi.org/10.1109/TNN.2004.832719 PubMed.CrossRefPubMedGoogle Scholar
  33. Izhikevich, E. M., & Edelman, G. M. (2008). Large-scale model of mammalian thalamocortical systems. Proceedings of the National Academy of Sciences of the United States of America, 105(9), 3593–3598.  https://doi.org/10.1073/pnas.0712231105 PubMed.CrossRefPubMedPubMedCentralGoogle Scholar
  34. Knight, B. W. (1972). Dynamics of encoding in a population of neurons. The Journal of general physiology, 59(6), 734–766.  https://doi.org/10.1085/jgp.59.6.734 PubMed.CrossRefPubMedPubMedCentralGoogle Scholar
  35. Kuznetsov, Y., (1998) Elements of Applied Bifurcation Theory: Springer-Verlag New York. 591 p.Google Scholar
  36. Lee, M. G., Manns, I. D., Alonso, A., & Jones, B. E. (2004). Sleep-Wake Related Discharge Properties of Basal Forebrain Neurons Recorded With Micropipettes in Head-Fixed Rats. Journal of Neurophysiology, 1182–1198.Google Scholar
  37. Lemieux, M., Chen, J.-Y., Lonjers, P., Bazhenov, M., & Timofeev, I. (2014). The Impact of Cortical Deafferentation on the Neocortical Slow Oscillation. The Journal of Neuroscience., 34(16), 5689–5703.  https://doi.org/10.1523/JNEUROSCI.1156-13.2014.CrossRefPubMedPubMedCentralGoogle Scholar
  38. Mainen, Z. F., Joerges, J., Huguenard, J. R., & Sejnowski, T. J. (1995). A model of spike initiation in neocortical pyramidal neurons. Neuron, 15(6), 1427–1439.  https://doi.org/10.1016/0896–6273(95)90020-9 PubMed.CrossRefPubMedGoogle Scholar
  39. Massimini, M., Huber, R., Ferrarelli, F., Hill, S., & Tononi, G. (2004). The Sleep Slow Oscillation as a Traveling Wave. The Journal of Neuroscience., 24(31), 6862–6870.  https://doi.org/10.1523/JNEUROSCI.1318-04.2004.CrossRefPubMedGoogle Scholar
  40. Massimini, M., Ferrarelli, F., Esser, S. K., Riedner, B. A., Huber, R., Murphy, M., et al. (2007). Triggering sleep slow waves by transcranial magnetic stimulation. Proceedings of the National Academy of Sciences., 104(20), 8496–8501.  https://doi.org/10.1073/pnas.0702495104.CrossRefGoogle Scholar
  41. McCormick, D. A. (1992). Neurotransmitter Actions in the Thalamus and Cerebral Cortex and Their Role in Neuromodulation of Thalamocortical Activity. Pogress in Nuerobiology, 39, 337–388 PubMed.CrossRefGoogle Scholar
  42. McCormick, D. A., Pape, H. C., & Williamson, A. (1991). Actions of norepinephrine in the cerebral cortex and thalamus: implications for function of the central noradrenergic system. Progress in Brain Research, 293–305.Google Scholar
  43. Molle, M., Marshall, L., Gais, S., & Born, J. (2002). Grouping of spindle activity during slow oscillations in human non-rapid eye movement sleep. Journal of Neuroscience, 10941–10947.Google Scholar
  44. Redman, S. (1990). Quantal Analysis of Synaptic Potentials in Neurons of the Central Nervous System. Physiological reviews, 70(1), 165–198 PubMed.CrossRefPubMedGoogle Scholar
  45. Rulkov, N. F. (2002). Modeling of spiking-bursting neural behavior using two-dimensional map. Physical Review E, 65(4), 041922.  https://doi.org/10.1103/PhysRevE.65.041922 PubMed.CrossRefGoogle Scholar
  46. Rulkov, N. F., & Bazhenov, M. (2008). Oscillations and Synchrony in Large-scale Cortical Network Models. Journal of Biological Physics, 34(3–4), 279–299.  https://doi.org/10.1007/s10867-008-9079-y PubMed.CrossRefPubMedPubMedCentralGoogle Scholar
  47. Rulkov, N. F., Timofeev, I., & Bazhenov, M. (2004). Oscillations in large-scale cortical networks: map-based model. Journal of Computational Neuroscience, 17(2), 203–223.  https://doi.org/10.1023/B:JCNS.0000037683.55688.7e PubMed.CrossRefPubMedGoogle Scholar
  48. Rulkov, N. F., Hunt, A. M., Rulkov, P. N., & Maximov, A. G. (2016). Quantization of Map-Based neuronal model for embedded simulations of neurobiological networks in real-time. American Journal of Engineering and Applied Sciences, 9(4), 973–984..  https://doi.org/10.3844/ajeassp 2016.973.984.
  49. Runfeldt, M. J., Sadovsky, A. J., & MacLean, J. N. (2014). Acetylcholine functionally reorganizes neocortical microcircuits. Journal of Neurophysiology, 112(5), 1205–16.Google Scholar
  50. Salin, P. A., & Prince, D. A. (1996). Spontaneous GABAA Receptor-Mediated Inhibitory Currents in Adult Rat Somatosensory Cortex. Journal of neurophysiology, 75(4), 1573–1588 PubMed.CrossRefPubMedGoogle Scholar
  51. Sanchez-Vives, M. V., & McCormick, D. A. (2000). Cellular and network mechanisms of rhythmic recurrent activity in neocortex. Nature neuroscience, 3(10), 1027–1034.  https://doi.org/10.1038/79848 PubMed PMID: Sanchez-Vives2000.CrossRefPubMedGoogle Scholar
  52. Sheroziya, M., & Timofeev, I. (2014). Global Intracellular Slow-Wave Dynamics of the Thalamocortical System. Journal of Neuroscience, 34(26), 8875–8893.  https://doi.org/10.1523/JNEUROSCI.4460-13.2014 PubMed.CrossRefPubMedPubMedCentralGoogle Scholar
  53. Shilnikov, A. L., & Rulkov, N. F. (2003). Origin of chaos in a two-dimensional map modeling spiking-bursting neural activity. Internation Journal of Bifurcation and Chaos, 13(11), 3325–3340 PubMed.Google Scholar
  54. Shilnikov, A. L., & Rulkov, N. F. (2004). Subthreshold oscillations in a map-based neuron model. Physics Letters A, 328(2–3), 177–184.  https://doi.org/10.1016/j.physleta.2004.05.062 PubMed.CrossRefGoogle Scholar
  55. Shu, Y., Hasenstaub, A., Badoual, M., Bal, T., & McCormick, D. A. (2003). Barrages of Synaptic Activity Control the Gain and Sensitivity of Cortical Neurons. The Journal of Neuroscience., 23(32), 10388–10401.PubMedGoogle Scholar
  56. Sigvardt, K. A., & Miller, W. L. (1998). Analysis and modeling of the locomotor central pattern generator as a network of coupled oscillators. Annals of the New York Academy of Sciences, 860, 250–265.  https://doi.org/10.1111/j.1749-6632.1998.tb09054.x PubMed.CrossRefPubMedGoogle Scholar
  57. Smith, G. D., & Sherman, S. M. (2002). Detectability of excitatory versus inhibitory drive in an integrate-and-fire-or-burst thalamocortical relay neuron model. The Journal of neuroscience : the official journal of the Society for Neuroscience, 22(23), 10242–10250 PubMed.Google Scholar
  58. Smith, G. D., Cox, C. L., Sherman, S. M., & Rinzel, J. (2000). Fourier analysis of sinusoidally driven thalamocortical relay neurons and a minimal integrate-and-fire-or-burst model. Journal of neurophysiology, 83(1), 588–610 PubMed.CrossRefPubMedGoogle Scholar
  59. Softky, W. R., & Koch, C. (1993). The highly irregular firing of cortical cells is inconsistent with temporal integration of random EPSPs. The Journal of Neuroscience, 13(1), 334–350 PubMed.Google Scholar
  60. Steriade, M., Nuñez, A., & Amzica, F. (1993a). A novel slow (<1 Hz) oscillation of neocortical neurons in vivo : depolarizing and hyperpolarizing components. The Journal of Neuroscience, 13, 3252–3265.PubMedGoogle Scholar
  61. Steriade, M., Nuez, A., & Amzica, F. (1993b). Intracellular analysis of relations between the slow (< 1 Hz) neocortical oscillation and other sleep rhythms of the electroencephalogram. The Journal of neuroscience, 13(8), 3266–3283 PubMed.PubMedGoogle Scholar
  62. Steriade, M., Contreras, D., Curro Dossi, R., & Nunez, A. (1993c). The Slow (<1 Hz) Oscillation in Reticular Thalamic and Thalamocortical Neurons: Scenario of Sleep Rhythm Generation in Interacting Thalamic and Neocortical Networks. The Journal of Neuroscience. p., 3284–3299.Google Scholar
  63. Steriade, M., McCormick, D. A., & Sejnowski, T. J. (1993d). Thalamocortical oscillations in the sleeping and aroused brain. Science, 262(5134), 679–685.CrossRefPubMedGoogle Scholar
  64. Steriade, M., Timofeev, I., & Grenier, F. (2001). Natural waking and sleep states: a view from inside neocortical neurons. Journal of neurophysiology, 85(5), 1969–1985.  https://doi.org/10.1016/j.neuroimage.2009.03.074 PubMed.CrossRefPubMedGoogle Scholar
  65. Tanabe, M., Ghwiler, B. H., & Gerber, U. (1998). L-Type Ca2+ channels mediate the slow Ca2+−dependent afterhyperpolarization current in rat CA3 pyramidal cells in vitro. Journal of neurophysiology, 80(5), 2268–2273 PubMed.CrossRefPubMedGoogle Scholar
  66. Timofeev, I., Bazhenov, M. (2005). Mechanisms and biological role of thalamocortical oscillations. Frank Columbus ed. Trends in Chronobiology Research: Nova Sceince Publishers, Inc.;p. 1-47.Google Scholar
  67. Timofeev, I., & Steriade, M. (1996). Low-frequency rhythms in the thalamus of intact-cortex and decorticated cats. Journal of Neurophysiology, 76(6), 4152–4168 PubMed.CrossRefPubMedGoogle Scholar
  68. Timofeev, I., Contreras, D., & Steriade, M. (1996). Synaptic responsiveness of cortical and thalamic neurones during various phases of slow sleep oscillation in cat. Journal of Physiology, 494(Pt 1), 265–278.Google Scholar
  69. Timofeev, I., Grenier, F., Bazhenov, M., Sejnowski, T. J., & Steriade, M. (2000a). Origin of slow cortical oscillations in deafferented cortical slabs. Cerebral cortex, 10(12), 1185–1199.  https://doi.org/10.1093/cercor/10.12.1185 PubMed.CrossRefPubMedGoogle Scholar
  70. Timofeev, I., Grenier, F., & Steriade, M. (2000b). Impact of intrinsic properties and synaptic factors on the activity of neocortical networks in vivo. J Physiol (Paris), 343–355.Google Scholar
  71. Timofeev, I., Grenier, F., & Steriade, M. (2001). Disfacilitation and active inhibition in the neocortex during the natural sleep-wake cycle: An intracellular study. Proceedings of the National Academy of Sciences., 98(4), 1924–1929.  https://doi.org/10.1073/pnas.98.4.1924.CrossRefGoogle Scholar
  72. Traub, R. D., Wong, R. K., Miles, R., & Michelson, H. (1991). A model of a CA3 hippocampal pyramidal neuron incorporating voltage-clamp data on intrinsic conductances. Journal of Neurophysiology, 66(2), 635–650 PubMed.CrossRefPubMedGoogle Scholar
  73. Tuckwell, H. C. (1988). Introduction to theoretical neurobiology (Vol. 2). Nonlinear and stochastic theries: Cambridge University Press.CrossRefGoogle Scholar
  74. Volgushev, M., Chauvette, S., Mukovski, M., & Timofeev, I. (2006). Precise Long-Range Synchronization of Activity and Silence in Neocortical Neurons during Slow-Wave Sleep. The Journal of Neuroscience., 26(21), 5665–5672.  https://doi.org/10.1523/JNEUROSCI.0279-06.2006.CrossRefPubMedGoogle Scholar
  75. Volgushev, M., Chauvette, S., & Timofeev, I. (2011). Long-range correlation of the membrane potential in neocortical neurons during slow oscillation. Progress in brain research, 193, 181–199.  https://doi.org/10.1016/B978-0-444-53839-0.00012-0 PubMed.CrossRefPubMedPubMedCentralGoogle Scholar
  76. Wei, Y., Krishnan, G. P., & Bazhenov, M. (2016). Synaptic Mechanisms of Memory Consolidation during Sleep Slow Oscillations. The Journal of Neuroscience., 36(15), 4231–4247.  https://doi.org/10.1523/jneurosci.3648-15.2016.CrossRefPubMedPubMedCentralGoogle Scholar
  77. Williams, T. L., & Bowtell, G. (1997). The calculation of frequency-shift functions for chains of coupled oscillators, with application to a network model of the lamprey locomotor pattern generator. Journal of Computational Neuroscience, 4(1), 47–55 PubMed.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Maxim Komarov
    • 1
  • Giri Krishnan
    • 1
  • Sylvain Chauvette
    • 2
  • Nikolai Rulkov
    • 3
  • Igor Timofeev
    • 2
    • 4
  • Maxim Bazhenov
    • 1
  1. 1.Department of MedicineUniversity of California San DiegoLa JollaUSA
  2. 2.Centre de recherche de l’Institut universitaire en santé mentale de Québec (CRIUSMQ)QCCanada
  3. 3.BioCircuits InstituteUniversity of CaliforniaLa JollaUSA
  4. 4.Department of Psychiatry and NeuroscienceUniversité LavalQuébecCanada

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