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Generative Biophysical Modeling of Dynamical Networks in the Olfactory System

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Olfactory Receptors

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1820))

Abstract

Generative models are computational models designed to generate appropriate values for all of their embedded variables, thereby simulating the response properties of a complex system based on the coordinated interactions of a multitude of physical mechanisms. In systems neuroscience, generative models are generally biophysically based compartmental models of neurons and networks that are explicitly multiscale, being constrained by experimental data at multiple levels of organization from cellular membrane properties to large-scale network dynamics. As such, they are able to explain the origins of emergent properties in complex systems, and serve as tests of sufficiency and as quantitative instantiations of working hypotheses that may be too complex to simply intuit. Moreover, when adequately constrained, generative biophysical models are able to predict novel experimental outcomes, and consequently are powerful tools for experimental design. We here outline a general strategy for the iterative design and implementation of generative, multiscale biophysical models of neural systems. We illustrate this process using our ongoing, iteratively developing model of the mammalian olfactory bulb. Because the olfactory bulb exhibits diverse and interesting properties at multiple scales of organization, it is an attractive system in which to illustrate the value of generative modeling across scales.

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References

  1. Chen WR, Shen GY, Shepherd GM, Hines ML, Midtgaard J (2002) Multiple modes of action potential initiation and propagation in mitral cell primary dendrite. J Neurophysiol 88:2755–2764

    Article  PubMed  Google Scholar 

  2. Pinching AJ, Powell TP (1971) The neuropil of the glomeruli of the olfactory bulb. J Cell Sci 9:347–377

    PubMed  CAS  Google Scholar 

  3. Shepherd GM, Greer CA (1998) Olfactory bulb. In: Shepherd GM (ed) The synaptic organization of the brain, 4th edn. Oxford University Press, New York

    Google Scholar 

  4. Skinner FK (2013) Moving beyond type I and type II neuron types. F1000Res 2:19

    PubMed  PubMed Central  Google Scholar 

  5. Colgin LL (2016) Rhythms of the hippocampal network. Nat Rev Neurosci 17:239–249

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Nagayama S, Homma R, Imamura F (2014) Neuronal organization of olfactory bulb circuits. Front Neural Circuits 8:98

    Article  PubMed  PubMed Central  Google Scholar 

  7. Soucy ER, Albeanu DF, Fantana AL, Murthy VN, Meister M (2009) Precision and diversity in an odor map on the olfactory bulb. Nat Neurosci 12:210–220

    Article  PubMed  CAS  Google Scholar 

  8. Cleland TA (2014) Construction of odor representations by olfactory bulb microcircuits. Prog Brain Res 208:177–203

    Article  PubMed  Google Scholar 

  9. Cleland TA, Sethupathy P (2006) Non-topographical contrast enhancement in the olfactory bulb. BMC Neurosci 7:7

    Article  PubMed  PubMed Central  Google Scholar 

  10. Mandairon N, Ferretti CJ, Stack CM, Rubin DB, Cleland TA, Linster C (2006) Cholinergic modulation in the olfactory bulb influences spontaneous olfactory discrimination in adult rats. Eur J Neurosci 24:3234–3244

    Article  PubMed  Google Scholar 

  11. Cleland TA, Chen S-YT, Hozer KW, Ukatu HN, Wong KJ, Zheng F (2012) Sequential mechanisms underlying concentration invariance in biological olfaction. Front Neuroeng 4:21

    Article  PubMed  PubMed Central  Google Scholar 

  12. Banerjee A, Marbach F, Anselmi F, Koh MS, Davis MB, Garcia da Silva P, Delevich K, Oyibo HK, Gupta P, Li B, Albeanu DF (2015) An interglomerular circuit gates glomerular output and implements gain control in the mouse olfactory bulb. Neuron 87:193–207

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Igarashi KM, Ieki N, An M, Yamaguchi Y, Nagayama S, Kobayakawa K, Kobayakawa R, Tanifuji M, Sakano H, Chen WR, Mori K (2012) Parallel mitral and tufted cell pathways route distinct odor information to different targets in the olfactory cortex. J Neurosci 32:7970–7985

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Fantana AL, Soucy ER, Meister M (2008) Rat olfactory bulb mitral cells receive sparse glomerular inputs. Neuron 59:802–814

    Article  PubMed  CAS  Google Scholar 

  15. Lepousez G, Nissant A, Bryant AK, Gheusi G, Greer CA, Lledo PM (2014) Olfactory learning promotes input-specific synaptic plasticity in adult-born neurons. Proc Natl Acad Sci U S A 111:13984–13989

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Mandairon N, Linster C (2009) Odor perception and olfactory bulb plasticity in adult mammals. J Neurophysiol 101:2204–2209

    Article  PubMed  Google Scholar 

  17. Pressler RT, Inoue T, Strowbridge BW (2007) Muscarinic receptor activation modulates granule cell excitability and potentiates inhibition onto mitral cells in the rat olfactory bulb. J Neurosci 27:10969–10981

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  18. Inoue T, Strowbridge BW (2008) Transient activity induces a long-lasting increase in the excitability of olfactory bulb interneurons. J Neurophysiol 99:187–199

    Article  PubMed  Google Scholar 

  19. Li G, Cleland TA (2013) A two-layer biophysical model of cholinergic neuromodulation in olfactory bulb. J Neurosci 33:3037–3058

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Rall W, Shepherd GM (1968) Theoretical reconstruction of field potentials and dendrodendritic synaptic interactions in olfactory bulb. J Neurophysiol 31:884–915

    Article  PubMed  CAS  Google Scholar 

  21. Lagier S, Carleton A, Lledo P-M (2004) Interplay between local GABAergic interneurons and relay neurons generates gamma oscillations in the rat olfactory bulb. J Neurosci 24:4382–4392

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  22. Neville KR, Haberly LB (2003) Beta and gamma oscillations in the olfactory system of the urethane-anesthetized rat. J Neurophysiol 90:3921–3930

    Article  PubMed  Google Scholar 

  23. Schoppa NE (2006) Synchronization of olfactory bulb mitral cells by precisely timed inhibitory inputs. Neuron 49:271–283

    Article  PubMed  CAS  Google Scholar 

  24. Schoppa NE (2006) AMPA/kainate receptors drive rapid output and precise synchrony in olfactory bulb granule cells. J Neurosci 26:12996–13006

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  25. Desmaisons D, Vincent JD, Lledo PM (1999) Control of action potential timing by intrinsic subthreshold oscillations in olfactory bulb output neurons. J Neurosci 19:10727–10737

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  26. Li G, Cleland TA (2017) A coupled-oscillator model of olfactory bulb gamma oscillations. PLoS Comput Biol 13(11):e1005760

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. David F, Courtiol E, Buonviso N, Fourcaud-Trocmé N (2015) Competing mechanisms of gamma and beta oscillations in the olfactory bulb based on multimodal inhibition of mitral cells over a respiratory cycle. eNeuro 2. https://doi.org/10.1523/ENEURO.0018-15.2015

  28. Osinski BL, Kay LM (2016) Granule cell excitability mediates gamma and beta oscillations in a model of the dendrodendritic microcircuit. J Neurophysiol 116:522–539

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Hayar A, Karnup S, Shipley MT, Ennis M (2004) Olfactory bulb glomeruli: external tufted cells intrinsically burst at theta frequency and are entrained by patterned olfactory input. J Neurosci 24:1190–1199

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  30. Hayar A, Karnup S, Ennis M, Shipley MT (2004) External tufted cells: a major excitatory element that coordinates glomerular activity. J Neurosci 24:6676–6685

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  31. Najac M, De Saint Jan D, Reguero L, Grandes P, Charpak S (2011) Monosynaptic and polysynaptic feed-forward inputs to mitral cells from olfactory sensory neurons. J Neurosci 31:8722–8729

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  32. Gire DH, Franks KM, Zak JD, Tanaka KF, Whitesell JD, Mulligan AA, Hen R, Schoppa NE (2012) Mitral cells in the olfactory bulb are mainly excited through a multistep signaling path. J Neurosci 32:2964–2975

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Marr D, Poggio T (1977) From understanding computation to understanding neural circuitry. Neurosciences Res Prog Bull 15:470–488

    Google Scholar 

  34. Harrison TA, Scott JW (1986) Olfactory bulb responses to odor stimulation: analysis of response pattern and intensity relationships. J Neurophysiol 56:1571–1589

    Article  PubMed  CAS  Google Scholar 

  35. Wellis DP, Scott JW, Harrison TA (1989) Discrimination among odorants by single neurons of the rat olfactory bulb. J Neurophysiol 61:1161–1177

    Article  PubMed  CAS  Google Scholar 

  36. Meredith M (1986) Patterned response to odor in mammalian olfactory bulb: the influence of intensity. J Neurophysiol 56:572–597

    Article  PubMed  CAS  Google Scholar 

  37. Aungst JL, Heyward PM, Puche AC, Karnup SV, Hayar A, Szabo G, Shipley MT (2003) Centre-surround inhibition among olfactory bulb glomeruli. Nature 426:623–629

    Article  PubMed  CAS  Google Scholar 

  38. Cleland TA, Johnson BA, Leon M, Linster C (2007) Relational representation in the olfactory system. Proc Natl Acad Sci U S A 104:1953–1958

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Koch C (1998) Biophysics of computation: information processing in single neurons. Oxford University Press, New York

    Google Scholar 

  40. Koch C, Segev I (eds) (1999) Methods in neuronal modeling: from ions to networks. Bradford, Cambridge, MA

    Google Scholar 

  41. Gerstner W, Kistler WM, Naud R, Paninski L (2014) Neuronal dynamics: from single neurons to networks and models of cognition. Cambridge University Press, Cambridge

    Book  Google Scholar 

  42. Rubin DB, Cleland TA (2006) Dynamical mechanisms of odor processing in olfactory bulb mitral cells. J Neurophysiol 96:555–568

    Article  PubMed  CAS  Google Scholar 

  43. Sethupathy P, Rubin DB, Li G, Cleland TA (2013) A model of electrophysiological heterogeneity in periglomerular cells. Front Comput Neurosci 7:49

    Article  PubMed  PubMed Central  Google Scholar 

  44. Rall W (1959) Branching dendritic trees and motoneuron membrane resistivity. Exp Neurol 1:491–527

    Article  PubMed  CAS  Google Scholar 

  45. Hodgkin AL, Huxley AF (1952) A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol 117:500–544

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Peace ST, Johnson BC, Li G, Kaiser M, Fukunaga I, Schaefer AT, Molnar AC, Cleland TA (2017) Coherent olfactory bulb gamma oscillations arise from coupling independent columnar oscillators. BioRxiv. https://doi.org/10.1101/213827

  47. Shen GY, Chen WR, Midtgaard J, Shepherd GM, Hines ML (1999) Computational analysis of action potential initiation in mitral cell soma and dendrites based on dual patch recordings. J Neurophysiol 82:3006–3020

    Article  PubMed  CAS  Google Scholar 

  48. Chen WR, Shepherd GM (1997) Membrane and synaptic properties of mitral cells in slices of rat olfactory bulb. Brain Res 745:189–196

    Article  PubMed  CAS  Google Scholar 

  49. Xiong W, Chen WR (2002) Dynamic gating of spike propagation in the mitral cell lateral dendrites. Neuron 34:115–126

    Article  PubMed  CAS  Google Scholar 

  50. Bhalla US, Bower JM (1993) Exploring parameter space in detailed single neuron models: simulations of the mitral and granule cells of the olfactory bulb. J Neurophysiol 69:1948–1965

    Article  PubMed  CAS  Google Scholar 

  51. Davison AP, Feng J, Brown D (2000) A reduced compartmental model of the mitral cell for use in network models of the olfactory bulb. Brain Res Bull 51:393–399

    Article  PubMed  CAS  Google Scholar 

  52. Bathellier B, Lagier S, Faure P, Lledo P-M (2006) Circuit properties generating gamma oscillations in a network model of the olfactory bulb. J Neurophysiol 95:2678–2691

    Article  PubMed  Google Scholar 

  53. Brea JN, Kay LM, Kopell NJ (2009) Biophysical model for gamma rhythms in the olfactory bulb via subthreshold oscillations. Proc Natl Acad Sci U S A 106:21954–21959

    Article  PubMed  PubMed Central  Google Scholar 

  54. Shao Z, Puche AC, Kiyokage E, Szabo G, Shipley MT (2009) Two GABAergic intraglomerular circuits differentially regulate tonic and phasic presynaptic inhibition of olfactory nerve terminals. J Neurophysiol 101:1988–2001

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. McQuiston AR, Katz LC (2001) Electrophysiology of interneurons in the glomerular layer of the rat olfactory bulb. J Neurophysiol 86:1899–1907

    Article  PubMed  CAS  Google Scholar 

  56. Kosaka K, Kosaka T (2005) Synaptic organization of the glomerulus in the main olfactory bulb: compartments of the glomerulus and heterogeneity of the periglomerular cells. Anat Sci Int 80:80–90

    Article  PubMed  Google Scholar 

  57. Kosaka K, Kosaka T (2007) Chemical properties of type 1 and type 2 periglomerular cells in the mouse olfactory bulb are different from those in the rat olfactory bulb. Brain Res 1167:42–55

    Article  PubMed  CAS  Google Scholar 

  58. Kiyokage E, Pan YZ, Shao Z, Kobayashi K, Szabo G, Yanagawa Y, Obata K, Okano H, Toida K, Puche AC, Shipley MT (2010) Molecular identity of periglomerular and short axon cells. J Neurosci 30:1185–1196

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Isaacson JS, Strowbridge BW (1998) Olfactory reciprocal synapses: dendritic signaling in the CNS. Neuron 20:749–761

    Article  PubMed  CAS  Google Scholar 

  60. Cang J, Isaacson JS (2003) In vivo whole-cell recording of odor-evoked synaptic transmission in the rat olfactory bulb. J Neurosci 23:4108–4116

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  61. Pinato G, Midtgaard J (2003) Regulation of granule cell excitability by a low-threshold calcium spike in turtle olfactory bulb. J Neurophysiol 90:3341–3351

    Article  PubMed  CAS  Google Scholar 

  62. Balu R, Larimer P, Strowbridge BW (2004) Phasic stimuli evoke precisely timed spikes in intermittently discharging mitral cells. J Neurophysiol 92:743–753

    Article  PubMed  Google Scholar 

  63. Cadetti L, Belluzzi O (2001) Hyperpolarisation-activated current in glomerular cells of the rat olfactory bulb. Neuroreport 12:3117–3120

    Article  PubMed  CAS  Google Scholar 

  64. Le Jeune H, Aubert I, Jourdan F, Quirion R (1995) Comparative laminar distribution of various autoradiographic cholinergic markers in adult main olfactory bulb. J Chem Neuroanat 9:99–112

    Article  PubMed  Google Scholar 

  65. Schoppa NE, Westbrook GL (1999) Regulation of synaptic timing in the olfactory bulb by an A-type potassium current. Nat Neurosci 2:1106–1113

    Article  PubMed  CAS  Google Scholar 

  66. Carnevale NT, Hines ML (2006) The neuron book. Cambridge University Press, Cambridge

    Book  Google Scholar 

  67. Bower JM, Beeman D (2003) The book of GENESIS: exploring realistic neural models with the GEneral NEural SImulation System, Internet edition. http://www.genesis-sim.org/GENESIS.

  68. Ray S, Bhalla US (2008) PyMOOSE: interoperable scripting in Python for MOOSE. Front Neuroinform 2:6

    PubMed  PubMed Central  Google Scholar 

  69. Vanier MC, Bower JM (1999) A comparative survey of automated parameter-search methods for compartmental neural models. J Comput Neurosci 7:149–171

    Article  PubMed  CAS  Google Scholar 

  70. Druckmann S, Banitt Y, Gidon A, Schurmann F, Markram H, Segev I (2007) A novel multiple objective optimization framework for constraining conductance-based neuron models by experimental data. Front Neurosci 1:7–18

    Article  PubMed  PubMed Central  Google Scholar 

  71. Rall W (1967) Distinguishing theoretical synaptic potentials computed for different soma-dendritic distributions of synaptic input. J Neurophysiol 30:1138–1168

    Article  PubMed  CAS  Google Scholar 

  72. Jack JJB, Noble D, Tsien RW (1975) Electric current flow in excitable cells. Clarendon Oxford, Oxford, UK

    Google Scholar 

  73. Destexhe A, Mainen ZF, Sejnowski TJ (1994) An efficient method for computing synaptic conductances based on a kinetic model of receptor binding. Neural Comput 6:14–18

    Article  Google Scholar 

  74. Wang XJ, Buzsáki G (1996) Gamma oscillation by synaptic inhibition in a hippocampal interneuronal network model. J Neurosci 16:6402–6413

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  75. Huang L, Ung K, Garcia I, Quast KB, Cordiner K, Saggau P, Arenkiel BR (2016) Task learning promotes plasticity of interneuron connectivity maps in the olfactory bulb. J Neurosci 36:8856–8871

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  76. Moreno MM, Bath K, Kuczewski N, Sacquet J, Didier A, Mandairon N (2012) Action of the noradrenergic system on adult-born cells is required for olfactory perceptual learning. J Neurosci 32:3748–3758

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  77. Gheusi G, Lledo PM (2014) Adult neurogenesis in the olfactory system shapes odor memory and perception. Prog Brain Res 208:157–175

    Article  PubMed  Google Scholar 

  78. Beshel J, Kopell N, Kay LM (2007) Olfactory bulb gamma oscillations are enhanced with task demands. J Neurosci 27:8358–8365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Doucette W, Restrepo D (2008) Profound context-dependent plasticity of mitral cell responses in olfactory bulb. PLoS Biol 6:e258

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Acknowledgments

NIDCD grants R03 DC013872 to G.L., R01 DC014701 and R01 DC014367 to T.A.C.

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Authors and Affiliations

  1. Department of Psychology, Cornell University, Ithaca, NY, USA

    Guoshi Li & Thomas A. Cleland

  2. Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA

    Guoshi Li

Authors
  1. Guoshi Li
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  2. Thomas A. Cleland
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Correspondence to Thomas A. Cleland .

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Editors and Affiliations

  1. Centro de Matemática Computação e Cognição (CMCC), Universidade Federal do ABC, São Bernardo do Campo, São Paulo, Brazil

    Fabio Marques Simoes de Souza

  2. Centro de Matemática Computação e Cognição (CMCC), Universidade Federal do ABC, São Bernardo do Campo, São Paulo, Brazil

    Gabriela Antunes

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Li, G., Cleland, T.A. (2018). Generative Biophysical Modeling of Dynamical Networks in the Olfactory System. In: Simoes de Souza, F., Antunes, G. (eds) Olfactory Receptors. Methods in Molecular Biology, vol 1820. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8609-5_20

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  • DOI: https://doi.org/10.1007/978-1-4939-8609-5_20

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-8608-8

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