Abstract
In this chapter, we present different methods to analyze intracellular recordings and the testing of these methods using dynamic-clamp techniques. The methods are derived from a model of synaptic background activity where the synaptic membrane conductances are considered as stochastic processes. Because this fluctuating point-conductance model can be treated analytically, different methods can be outlined to estimate different characteristics of synaptic noise from the membrane potential (V m) activity, such as the mean and variance of the excitatory and inhibitory conductance distributions (the VmD method) or spike-triggered averages of conductances. These analysis methods can be validated in controlled conditions using dynamic-clamp injection of known synaptic conductance patterns, as we illustrate here. Our approach constitutes a novel application of the dynamic clamp, which could be extended to the testing of other methods for extracting conductance information from the recorded V m activity of neurons.
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References
Anderson JS, Carandini M, Ferster D (2000) Orientation tuning of input conductance, excitation, and inhibition in cat primary visual cortex. J Neurophysiol 84:909–926.
Baranyi A, Szente MB, Woody CD (1993) Electrophysiological characterization of different types of neurons recorded in vivo in the motor cortex of the cat. II. Membrane parameters, action potentials, current-induced voltage responses and electrotonic structures. J Neurophysiol 69:1865–1879.
Bedard C, Destexhe A (2008) A modified cable formalism for modeling neuronal membranes at high frequencies. Biophys J 94:1133–1143.
Borg-Graham LJ, Monier C, Frégnac Y (1998) Visual input evokes transient and strong shunting inhibition in visual cortical neurons. Nature 393:369–373.
Brette R, Piwkowska Z, Monier C, Rudolph-Lilith M, Fournier J, Levy M, Fregnac Y, Bal T, Destexhe A (2008) High-resolution intracellular recordings using a real-time computational model of the electrode. Neuron, 59:379–391.
Crochet S, Petersen CC (2006) Correlating whisker behavior with membrane potential in barrel cortex of awake mice. Nat Neurosci 9:608–610.
Cunningham MO, Pervouchine DD, Racca C, Kopell NJ, Davies CH, Jones RS, Traub RD, Whittington M (2006) Neuronal metabolism governs cortical network response state. Proc Natl Acad Sci USA 103:5597–5601.
Destexhe A, Paré D (1999) Impact of network activity on the integrative properties of neocortical pyramidal neurons in vivo. J Neurophysiol 81:1531–1547.
Destexhe A, Rudolph M, Fellous J-M, Sejnowski TJ (2001) Fluctuating synaptic conductances recreate in vivo-like activity in neocortical neurons. Neuroscience 107:13–24.
Destexhe A, Rudolph M (2004) Extracting information from the power spectrum of synaptic noise. J Comput Neurosci 17:327–345.
Destexhe A, Hughes SW, Rudolph M, Crunelli V (2007) Are corticothalamic “up” states fragments of wakefulness? Trends Neurosci 30:334–342.
Harsch A, Robinson HP (2000) Postsynaptic variability of firing in rat cortical neurons: the roles of input synchronization and synaptic NMDA receptor conductance. J Neurosci 20:6181–6192.
Hughes SW, Lorincz M, Cope DW, Crunelli V (2008) NeuReal: An interactive simulation system for implementing artificial dendrites and large hybrid networks. J Neurosci Methods 169:290–301.
Le Masson G, Renaud-Le Masson S, Sharp AA, Marder E, Abbott LF (1992) Real-time interaction between a model neuron and the crustacean stomatogastric nervous system In: Society for Neuroscience Meeting. 18, 1055.
Lee AK, Manns ID, Sakmann B, Brecht M (2006) Whole-cell recordings in freely moving rats. Neuron 51:399–407.
Leger J-F, Stern EA, Aertsen A, Heck D (2005) Synaptic integration in rat frontal cortex shaped by network activity. J Neurophysiol 93:281–293.
Lindner B, Longtin A (2006) Comment on “Characterization of subthreshold voltage fluctuations in neuronal membranes”, by M. Rudolph and A. Destexhe. Neural Comput 18:1896–1931.
Margrie TW, Brecht M, Sakmann B (2002) In vivo, low-resistance, whole-cell recordings from neurons in the anaesthetized and awake mammalian brain. Pflugers Arch 444:491–498.
Matsumura M, Cope T, Fetz EE (1988) Sustained excitatory synaptic input to motor cortex neurons in awake animals revealed by intracellular recording of membrane potentials. Exp Brain Res 70:463–469.
McCormick DA, Shu Y, Hasenstaub A, Sanchez-Vives M, Badoual M, Bal T (2003) Persistent cortical activity: mechanisms of generation and effects on neuronal excitability. Cereb Cortex 13:1219–1231.
Metherate R, Ashe JH (1993) Ionic flux contributions to neocortical slow waves and nucleus basalis-mediated activation:whole-cell recordings in vivo. J Neurosci 13:5312–5323.
Monier C, Chavane F, Baudot P, Graham LJ, Frégnac Y (2003) Orientation and direction selectivity of synaptic inputs in visual cortical neurons: a diversity of combinations produces spike tuning. Neuron 37:663–680.
Monier C, Fournier J, Frégnac Y (2008) In vitro and in vivo measures of evoked excitatory and inhibitory conductance dynamics in sensory cortices. J Neurosci Meth 169:323–365.
Okun M, Lampl I (2008) Instantaneous correlation of excitation and inhibition during ongoing and sensory-evoked activities. Nat Neurosci 11:535–537.
Paré D, Shink E, Gaudreau H, Destexhe A, Lang EJ (1998) Impact of spontaneous synaptic activity on the resting properties of cat neocortical neurons in vivo. J Neurophysiol 79:1450–1460.
Piwkowska Z, Rudolph M, Badoual M, Destexhe A, Bal T (2005) Re-creating active states in vitro with a dynamic-clamp protocol. Neurocomputing 65–66:55–60.
Piwkowska Z, Pospischil M, Brette R, Sliwa J, Rudolph-Lilith M, Bal T, Destexhe A. (2008) Characterizing synaptic conductance fluctuations in cortical neurons and their influence on spike generation. J Neurosci Meth 169:302–322.
Pospischil M, Piwkowska Z, Rudolph M, Bal T, Destexhe A (2007) Calculating event-triggered average synaptic conductances from the membrane potential. J Neurophysiol 97:2544–2552.
Press WH, Flannery BP, Teukolsky SA, Vetterling WT (1986) Numerical Recipes. The Art of Scientific Computing. Cambridge, MA: Cambridge University Press.
Richardson MJ (2004) Effects of synaptic conductance on the voltage distribution and firing rate of spiking neurons. Phys Rev E Stat Nonlin Soft Matter Phys 69:051918.
Robinson HP, Kawai N (1993) Injection of digitally synthesized synaptic conductance transients to measure the integrative properties of neurons. J Neurosci Methods 49:157–165.
Rudolph M, Destexhe A (2003) Characterization of subthreshold voltage fluctuations in neuronal membranes. Neural Comput 15:2577–2618.
Rudolph M, Piwkowska Z, Badoual M, Bal T, Destexhe A (2004) A method to estimate synaptic conductances from membrane potential fluctuations. J Neurophysiol 91:2884–2896.
Rudolph M, Destexhe (2005). An extended analytic expression for the membrane potential distribution of conductancebased synaptic noise. Neural Comput 17:2301–2315.
Rudolph M, Pelletier J-G, Paré D, 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.
Rudolph M, Destexhe A (2006) On the use of analytic expressions for the voltage distribution to analyze intracellular recordings. Neural Comput 18: 2917–2922.
Rudolph M, Pospischil M, Timofeev I, Destexhe A (2007) Inhibition determines membrane potential dynamics and controls action potential generation in awake and sleeping cat cortex. J Neurosci 27:5280–5290.
Sanchez-Vives MV, McCormick DA (2000) Cellular and network mechanisms of rhythmic recurrent activity in neocortex. Nat Neurosci 3:1027–1034.
Sanchez-Vives MV, Nowak LG, McCormick DA (2000) Cellular mechanisms of long-lasting adaptation in visual cortical neurons in vitro. J Neurosci 20:4286–4299.
Silberberg G, Wu C, Markram H (2004) Synaptic dynamics control the timing of neuronal excitation in the activated neocortical microcircuit. J Physiol 556:19–27.
Sharp AA, O’Neil MB, Abbott LF, Marder E (1993) Dynamic clamp: computer-generated conductances in real neurons. J Neurophysiol 69:992–995.
Shu Y, Hasenstaub A, Badoual M, Bal T, McCormick DA (2003) Barrages of synaptic activity control the gain and sensitivity of cortical neurons. J Neurosci 23:10388–10401.
Steriade M, Nunez A, Amzica F (1993) A novel slow (< 1 Hz) oscillation of neocortical neurons in vivo: depolarizing and hyperpolarizing components. J Neurosci 13:3252–3265.
Steriade M, Timofeev I, Grenier F (2001) Natural waking and sleep states: a view from inside neocortical neurons. J Neurophysiol 85:1969–1985.
Timofeev I, Grenier F, Steriade M (2001) Disfacilitation and active inhibition in the neocortex during the natural sleepwake cycle: an intracellular study. Proc Natl Acad Sci USA 98:1924–1929.
Uhlenbeck GE and Ornstein LS (1930) On the theory of the Brownian motion. Phys Rev 36:823–841.
Wehr M, Zador AM (2003) Balanced inhibition underlies tuning and sharpens spike timing in auditory cortex. Nature 426:442–446.
Wilent W, Contreras D (2005) Dynamics of excitation and inhibition underlying stimulus selectivity in rat somatosensory cortex. Nature Neurosci 8:1364–1370.
Williams SR (2004) Spatial compartmentalization and functional impact of conductance in pyramidal neurons. Nat Neurosci 7:961–967.
Williams SR (2005) Encoding and decoding of dendritic excitation during active states in pyramidal neurons. J Neurosci 25:5894–5902.
Woody CD, Gruen E (1978) Characterization of electrophysiological properties of intracellularly recorded neurons in the neocortex of awake cats: a comparison of the response to injected current in spike overshoot and undershoot neurons. Brain Res 158:343–357.
Acknowledgments
Research supported by CNRS, ANR, ACI, HFSP, and the European Community (FACETS grant FP6 15879). Z.P. gratefully acknowledges the support of the FRM.
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Piwkowska, Z., Pospischil, M., Rudolph-Lilith, M., Bal, T., Destexhe, A. (2009). Testing Methods for Synaptic Conductance Analysis Using Controlled Conductance Injection with Dynamic Clamp. In: Bal, T., Destexhe, A. (eds) Dynamic-Clamp. Springer Series in Computational Neuroscience, vol 1. Springer, New York, NY. https://doi.org/10.1007/978-0-387-89279-5_6
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DOI: https://doi.org/10.1007/978-0-387-89279-5_6
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