Dynamic-Clamp pp 287-320 | Cite as

Re-Creating In Vivo-Like Activity and Investigating the Signal Transfer Capabilities of Neurons: Dynamic-Clamp Applications Using Real-Time Neuron

  • Gerard Sadoc
  • Gwendal Le Masson
  • Bruno Foutry
  • Yann Le Franc
  • Zuzanna Piwkowska
  • Alain Destexhe
  • Thierry Bal
Part of the Springer Series in Computational Neuroscience book series (NEUROSCI, volume 1)


Understanding the input–output transfer properties of NEURONs is a complex problem which requires detailed knowledge of the intrinsic properties of neurons, and how these intrinsic properties influence signal integration. More recently, it became clear that the transfer function of neurons also highly depends on the activity of the surrounding network, and in particular on the presence of synaptic background activity. We review here different in vitro techniques to investigate such problems in cortex, thalamus, and spinal cord, along three examples: First, by constructing “hybrid” networks with real and artificial thalamic neurons using dynamic clamp, it was possible to study how the state of the circuit influences spike transfer through the thalamus. Second, the dynamic clamp was used to study how the state of discharge of spinal neurons influences their information processing capabilities. Third, the dynamic-clamp experiments could re-create “in vivo-like” background synaptic activity by injection of stochastic excitatory and inhibitory conductances, and we showed that this activity profoundly modifies the input–output transfer function of thalamic and cortical neurons. We also illustrate how such applications are greatly facilitated by the use of a neuronal simulator to run the dynamic-clamp experiments, as shown here for RT-NEURON.


Digital Signal Processor Thalamic Neuron Synaptic Conductance Inhibitory Conductance Dynamic Clamp 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported by Centre National de la Recherche Scientifique, European Commission (IST-2001-34712), Action Concertée Incitative “Neurosciences intégratives et computationnelles” and ANR grants T-State and HR-cortex. We thank Michelle Rudolph, Paul Galloux, Leonel Gomez, and José Gomez for help with computation, Jakob Wolfart, Damien Debay, and Mathilde Badoual for testing RT-NEURON experimentally, and Charlotte Deleuze for comments on the manuscript.


  1. Ahlsen G, Lindstrom S and Lo FS (1985) Interaction between inhibitory pathways to principal cells in the lateral geniculate nucleus of the cat. Exp Brain Res 58: 134–143.PubMedCrossRefGoogle Scholar
  2. Azouz R and Gray CM (1999) Cellular mechanisms contributing to response variability of cortical neurons in vivo. J Neurosci 19:2209–23.PubMedGoogle Scholar
  3. Bal T, Von Krosigk M and Mccormick DA (1995) Synaptic and membrane mechanisms underlying synchronized oscillations in the ferret lateral geniculate nucleus in vitro. J Physiol 483: 641–663.PubMedGoogle Scholar
  4. Bernander O, Douglas RJ, Martin KAC and Koch C (1991) Synaptic background activity influences spatiotemporal integration in single pyramidal cells. Proc Natl Acad Sci USA 88:11569–11573.PubMedCrossRefGoogle Scholar
  5. Brette R, Piwkowska Z, Monier C, Rudolph-Lilith M, Fournier J, Levy M, Frégnac Y, Bal T and Destexhe A (2008) High-resolution intracellular recordings using a real-time computational model of the electrode. Neuron 59:379–391.PubMedCrossRefGoogle Scholar
  6. Bringuier V, Frégnac Y, Baranyi A, Debanne D and Shulz D (1997) Synaptic origin and stimulus dependency of neuronal oscillatory activity in the primary visual cortex of the cat. J Physiol (Lond) 500:751–74.Google Scholar
  7. Bringuier V, Chavane F, Glaeser L and Frégnac Y (1999) Horizontal propagation of visual activity in the synaptic integration field of area 17 neurons. Science 283:695–699.PubMedCrossRefGoogle Scholar
  8. Chance FS, Abbott LF and Reyes AD (2002) Gain modulation from background synaptic input. Neuron 35:773–782.PubMedCrossRefGoogle Scholar
  9. Contreras D, Destexhe A, Sejnowski TJ and Steriade M (1996a) Control of spatiotemporal coherence of a thalamic oscillation by corticothalamic feedback. Science 274:771–774.Google Scholar
  10. Contreras D, Timofeev I and Steriade M (1996b) Mechanisms of long-lasting hyperpolarizations underlying slow sleep oscillations in cat corticothalamic networks. PG – 251–64. J Physiol 494:251–64.Google Scholar
  11. Crick F, (1984) Function of the thalamic reticular complex: The searchlight hypothesis. Proc Natl Acad Sci USA 81:4586–4590.PubMedCrossRefGoogle Scholar
  12. Debay D, Wolfart J, Le Franc Y, Le Masson G and Bal T (2004) Exploring spike transfer through the thalamus using hybrid artificial-biological neuronal networks. J Physiol Paris 98:540–558.PubMedCrossRefGoogle Scholar
  13. Derjan D, Bertrand B, Le Masson G, Landry M, Morrisset V and Nagy F (2003) Multiple states in spinal dorsal Horn neurons : switch under a dynamic balance of metabotropic controls. Nat Neurosci 6:274–281.CrossRefGoogle Scholar
  14. Destexhe A and Contreras D (2006) Neuronal computations with stochastic network states. Science 314:85–90.PubMedCrossRefGoogle Scholar
  15. Destexhe A and Paré D (1999) Impact of network activity on the integrative properties of neocortical pyramidal neurons in vivo. J Neurophysiol 81:1531–1547.PubMedGoogle Scholar
  16. Destexhe A, Rudolph M and Pare D (2003), The high-conductance state of neocortical neurons in vivo. Nat Rev Neurosci 4:739–751.PubMedCrossRefGoogle Scholar
  17. Destexhe A, Rudolph M, Fellous JM and Sejnowski TJ (2001) Fluctuating synaptic conductances recreate in-vivo-like activity in neocortical neurons. Neuroscience 107:13–24.PubMedCrossRefGoogle Scholar
  18. Destexhe, A and Sejnowski, TJ (2003) Interactions between membrane conductances underlying thalamocortical slow-wave oscillations. Physiol Rev 83:1401–1453.PubMedGoogle Scholar
  19. Dorval AD, Christini DJ and White JA (2001) Real-time Linux dynamic clamp: a fast and flexible way to construct virtual ion channels in living cells. Ann Biomed Eng 29:897–907.PubMedCrossRefGoogle Scholar
  20. Guido W and Weyand T (1995) Burst responses in thalamic relay cells of the awake behaving cat. J Neurophysiol 74:1782–1786.PubMedGoogle Scholar
  21. Hines ML and Carnevale NT (1997) The NEURON simulation environment. Neural Comput 9:1179–1209.PubMedCrossRefGoogle Scholar
  22. Hirsch JC, Fourment A and Marc ME (1983) Sleep-related variations of membrane potential in the lateral geniculate body relay neurons of the cat. Brain Res 259:308–312.PubMedCrossRefGoogle Scholar
  23. Hô N and Destexhe A (2000) Synaptic background activity enhances the responsiveness of neocortical pyramidal neurons. J Neurophysiol 84:1488–1496.PubMedGoogle Scholar
  24. Hodgkin AL and Huxley AF (1952) A quantitative description of membrane current and its application to conduction and excitation in nerve. J. Physiol. 117:500–544.PubMedGoogle Scholar
  25. Hughes SW, Lőrincz ML, Cope DW et al. (2008) NeuReal: An interactive simulation system for implementing artificial dendrites and large hybrid networks. J Neurosci Methods 169:290–301.PubMedCrossRefGoogle Scholar
  26. Hultborn H, Lindstrom S and Wigstrom H (1979) On the function of recurrent inhibition in the spinal cord. Exp Brain Res 37:399–403.PubMedCrossRefGoogle Scholar
  27. Jahnsen H and Llinas R (1984) Electrophysiological properties of guinea pig thalamic neurones: an in vitro study. J Physiol (London) 349:205–226.Google Scholar
  28. Kim U, Sanchez-Vives MV and McCormick DA (1997) Functional dynamics of GABAergic inhibition in the thalamus. Science 278:130–134.PubMedCrossRefGoogle Scholar
  29. Koch C (1987) The action of the corticofugal pathway on sensory thalamic nuclei: a hypothesis, Neuroscience 23:399–406.PubMedCrossRefGoogle Scholar
  30. Le Franc Y, Foutry B, Nagy F and Le Masson G (2001) Nociceptive signal transfer through the dorsal horn network: hybrid and dynamic-clamp approaches using a real-time implementation of the NEURON simulation environment. Soc Neurosci Abstracts 927:18.Google Scholar
  31. Le Masson G, Renaud-Le Masson S, Debay D and Bal T (2002) Feedback inhibition controls spike transfer in hybrid thalamic circuits. Nature 417:854–858.PubMedCrossRefGoogle Scholar
  32. Le Masson S, Laflaquière A, Bal T and Le Masson G (1999) Analog circuits for modeling biological neural networks: Design and applications. IEEE Trans Biomed Eng 45:638–645.CrossRefGoogle Scholar
  33. Llinas R (1988) The intrinsic electrophysiological properties of mammalian neurons: insights into central nervous system function. Science 242:1654–1664.PubMedCrossRefGoogle Scholar
  34. Marre O, El Boustani S, Baudot P, Levy M, Monier C, Huguet N, Pananceau M, Fournier J, Destexhe A. Fregnac Y. (2007) Stimulus-dependency of spectral scaling laws in V1 synaptic activity as a read-out of the effective network topology. Abstr Soc Neurosci 33:790.6.Google Scholar
  35. Mcclurkin JW, Optican LM and Richmond BJ (1994) Cortical feedback increases visual information transmitted by monkey parvocellular lateral geniculate nucleus neurons. Vis Neurosci 11:601–617.PubMedCrossRefGoogle Scholar
  36. McCormick DA and Bal T (1997) Sleep and arousal: thalamocortical mechanisms. Annu Rev Neurosci 20:185–215.PubMedCrossRefGoogle Scholar
  37. McCormick DA and Feeser HR (1990) Functional implications of burst firing and single spike activity in lateral geniculate relay neurons. Neuroscience 39:103–113.PubMedCrossRefGoogle Scholar
  38. McCormick DA (1992) Neurotransmitter actions in the thalamus and cerebral cortex and their role in neuromodulation of thalamocortical activity. Prog Neurobiol 39:337–388.PubMedCrossRefGoogle Scholar
  39. Milescu LS, Yamanishi T, Ptak K, Mogri MZ and Smith JC (2008) Real-time kinetic modeling of voltage-gated ion channels using dynamic clamp. Biophys J 95:66–87.PubMedCrossRefGoogle Scholar
  40. Montero VM (1999) Amblyopia decreases activation of the corticogeniculate pathway and visual thalamic reticularis in attentive rats: a ‘focal attention’ hypothesis. Neuroscience 91:805–817.PubMedCrossRefGoogle Scholar
  41. Morisset V and Nagy F (1998) Nociceptive integration in the rat spinal cord: role of nonlinear membrane properties of deep dorsal horn neurons. Eur J Neurosci 10:3642–3652.PubMedCrossRefGoogle Scholar
  42. Mumford D (1991) On the computational architecture of the neocortex. I. The role of the thalamo-cortical loop. Biol Cybern 65:135–145.PubMedCrossRefGoogle Scholar
  43. Murphy PC and Sillito AM (1987) Corticofugal feedback influences the generation of length tuning in the visual pathway. Nature 329:727–729.PubMedCrossRefGoogle Scholar
  44. Paré D, Shink E., Gaudreau H, Destexhe A and Lang, EJ (1998) Impact of spontaneous synaptic activity on the resting properties of cat neocortical neurons in vivo. J. Neurophysiol. 79:1450–1460.PubMedGoogle Scholar
  45. Piwkowska Z, Pospischil M, Brette R, Sliwa J, Rudolph-Lilith M, Bal T and Destexhe A (2008) Characterizing synaptic conductance fluctuations in cortical neurons and their influence on spike generation. J Neurosci Methods 169(2):302–22.PubMedCrossRefGoogle Scholar
  46. Pospischil M, Piwkowska Z, Rudolph M, Bal T and Destexhe A (2007) Calculating event-triggered average synaptic conductances from the membrane potential. J Neurophysiol 97:2544–2552PubMedCrossRefGoogle Scholar
  47. Prescott SA and De Koninck Y (2003) Gain control of firing rate by shunting inhibition: roles of synaptic noise and dendritic saturation. Proc Natl Acad Sci USA 100:2076–2081.PubMedCrossRefGoogle Scholar
  48. Prinz AA, Abbott LF and Marder E (2004) The dynamic clamp comes of age. Trends Neurosci 27:218–224.PubMedCrossRefGoogle Scholar
  49. Przybyszewski AW, Gaska JP, Foote W and Pollen DA (2000) Striate cortex increases contrast gain of macaque LGN neurons. Vis Neurosci 17:485–494.PubMedCrossRefGoogle Scholar
  50. Ramcharan EJ, Cox CL, Zhan XJ, Sherman SM and Gnadt JW (2000a) Cellular mechanisms underlying activity patterns in the monkey thalamus during visual behavior. J Neurophysiol 84:1982–1987.Google Scholar
  51. Ramcharan EJ, Gnadt JW and Sherman SM (2000b) Burst and tonic firing in thalamic cells of unanesthetized, behaving monkeys. Vis Neurosci 17:55–62.Google Scholar
  52. Robinson, HPC (2008) A scriptable DSP-based system for dynamic conductance injection. J Neurosci Methods 169:271–281.PubMedCrossRefGoogle Scholar
  53. Rudolph M, Piwkowska Z, Badoual M, Bal T and Destexhe A (2004) A method to estimate synaptic conductances from membrane potential fluctuations. J Neurophysiol 91:2884–2896.PubMedCrossRefGoogle Scholar
  54. Rudolph M and Destexhe A (2003) A fast-conducting, stochastic integrative mode for neocortical neurons in vivo. J Neurosci 23:2466–2476.PubMedGoogle Scholar
  55. Rudolph M, Pelletier J-G, Pare D and Destexhe A (2005) Characterization of synaptic conductances and integrative properties during electrically-induced EEG-activated states in neocortical neurons in vivo. J Neurophysiol 94:2805–2821.PubMedCrossRefGoogle Scholar
  56. Sherman SM and Guillery RW (2002) The role of the thalamus in the flow of information to the cortex. Philos Trans R Soc Lond B Biol Sci 357:1695–1708.PubMedCrossRefGoogle Scholar
  57. Sherman SM and Koch C (1986), The control of retinogeniculate transmission in the mammalian lateral geniculate nucleus. Exp Brain Res 63:1–20.PubMedCrossRefGoogle Scholar
  58. Sherman SM (2001a) Tonic and burst firing: dual modes of thalamocortical relay. Trends Neurosci 24:122–126.Google Scholar
  59. Sherman SM (2001b) A wake-up call from the thalamus. Nat Neurosci 4:344–346.Google Scholar
  60. Shu Y, Hasenstaub AR, Badoual M, Bal T and McCormick DA (2003) Barrage of synaptic activity control the gain and sensitivity of cortical neurons. J Neurosci 23:10388–10401.PubMedGoogle Scholar
  61. Sillito AM and Jones HE (2002) Corticothalamic interactions in the transfer of visual information. Philos Trans R Soc Lond B Biol Sci 357:1739–1752.PubMedCrossRefGoogle Scholar
  62. Sillito AM, Cudeiro J and Murphy PC (1993) Orientation sensitive elements in the corticofugal influence on centre-surround interactions in the dorsal lateral geniculate nucleus. Exp Brain Res 93:6–16.PubMedCrossRefGoogle Scholar
  63. Sillito AM, Jones HE, Gerstein GL and West DC (1994) Feature-linked synchronization of thalamic relay cell firing induced by feedback from the visual cortex. Nature 369:479–482.PubMedCrossRefGoogle Scholar
  64. Steriade M (2001) Impact of network activities on neuronal properties in corticothalamic systems. J Neurophysiol 86:1–39.PubMedGoogle Scholar
  65. Steriade M, Mccormick DA and Sejnowski TJ (1993), Thalamocortical oscillations in the sleeping and aroused brain. Science 262:679–685.PubMedCrossRefGoogle Scholar
  66. Steriade M and McCarley RW (1990) Brainstem Control of Wakefulness and Sleep. New York: Plenum Press.Google Scholar
  67. Steriade M, Jones, EG and McCormick DA (1997) Thalamus (eds. Steriade, M, Jones, EG & McCormick, DA) (Elsevier Science Ltd, Amsterdam, Lausanne, New York, Oxford, Shannon, Tokyo).Google Scholar
  68. Swadlow HA and Gusev AG (2001) The impact of ‘bursting’ thalamic impulses at a neocortical synapse. Nat Neurosci 4:402–408.PubMedCrossRefGoogle Scholar
  69. Temereanca S and Simons DJ (2004) Functional topography of corticothalamic feedback enhances thalamic spatial response tuning in the somatosensory whisker/barrel system. Neuron 41:639–651.PubMedCrossRefGoogle Scholar
  70. Timofeev I, Contreras D and Steriade M (1996) Synaptic responsiveness of cortical and thalamic neurones during various phases of slow sleep oscillation in cat. J Physiol 494:265–278.PubMedGoogle Scholar
  71. Tuckwell HC (1988) Introduction to Theoretical Neurobiology. Cambridge University Press, Cambridge UK.CrossRefGoogle Scholar
  72. von Krosigk M, Bal T and McCormick DA (1993) Cellular mechanisms of a synchronized oscillation in the thalamus. Science 261: 361–364.CrossRefGoogle Scholar
  73. Williams SR (2004) Spatial compartmentalization and functional impact of conductance in pyramidal neurons. Nat Neurosci 7:961–967.PubMedCrossRefGoogle Scholar
  74. Williams SR and Mitchell SJ (2008) Direct measurement of somatic voltage clamp errors in central neurons. Nat Neurosci 11:790–798.PubMedCrossRefGoogle Scholar
  75. Wolfart J, Debay D, Le Masson G, Destexhe A and Bal T (2005) Synaptic background activity controls spike transfer from thalamus to cortex. Nat Neurosci 8:1760–1767.PubMedCrossRefGoogle Scholar
  76. Yingling CD and Skinner JE (1977)Gating of Thalamic Input to Cerebral Cortex by Nucleus Reticularis Thalami, vol. 1, Karger, Basel.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Gerard Sadoc
    • 1
  • Gwendal Le Masson
  • Bruno Foutry
  • Yann Le Franc
  • Zuzanna Piwkowska
  • Alain Destexhe
  • Thierry Bal
  1. 1.CNRSFrance

Personalised recommendations