Abstract
How do the properties of signalling molecules constrain the structure and function biological networks such as those of our brain? Here we focus on the action potential, the fundamental electrical signal of the brain, because malfunction of the action potential causes many neurological conditions. The action potential is mediated by the concerted action of voltagegated ion channels and relating the properties of these signalling molecules to the properties of neurons at the systems level is essential for biomedical brain research, as minor variations in properties of a neurons individual component, can have large, pathological effects on the physiology of the whole nervous system and the behaviour it generates. This approach is very complex and requires us to discuss computational methods that can span across many levels of biological organization, from single signalling proteins to the organization of the entire nervous system, and encompassing time scales from milliseconds to hours.Within this methodical framework, we will focus on how the properties of voltagegated ion channels relate to the functional and structural requirements of axonal signalling and the engineering design principles of neurons and their axons (nerve fibres). This is important, not only because axons are the essential wires that allow information transmission between neurons, but also because they play a crucial in neural computation itself.
Many properties at the molecular level of the nervous system display noise and variability, which in turn makes it difficult to understand neuronal design and behaviour at the systems level without incorporating the sources of this probabilistic behaviour. To this end we have developed computationalmethods, which will enable us to conduct stochastic simulations of neurons that account for the probabilistic behaviour of ion channels. This allows us to explore the relationship between individual ion channel properties, derived from high-resolution patch clamp data,and the properties of axons. The computational techniques we introduce here will allow us to tackle problems that are (1) beyond the reach of experimental methods, because we can disambiguate the effects of variability and reliability of individual molecular components to whole cell behaviour, and (2) allow us to consider the many finer fibers in the central and peripheral system, which are experimentally difficulty to access and record from. We start with the well-established data that Ion channels behave with an element of randomness resulting in “channel noise”. The impact of channel noise in determining axonal structure and function became apparent only very recently, because in the past findings were extrapolated from very large unmyelinated axons (squid giant axon), where channel noise had little impact due to the law of large numbers. However, the many axons in the central and peripheral nervous system are over 1,000 times thinner and the small number of ion channels involved in sustaining the action potential, imply that channel noise can affect signalling and constraint both the reliability of neural circuit function, but also sets limits to the anatomy of the brain as a whole.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Notes
- 1.
On the other side brains and organisms build themselves from themselves.
- 2.
but, consider the following reflections of our nervous system’s variability: the little random motions of a pointed finger, our uncertainty when try to understand a conversation in the presence of loud background noise, or when we seem not able to see our keys that were in plain view when we were searching for them.
- 3.
We ignore here synaptic input as a form of electrical “noise” and note that the common use of the term “synaptic background noise” denotes the (not necessarily random) variability produced by massive synaptic input in cortical neurons (Faisal et al. 2008).
- 4.
using the Gillespie algorithm described.
References
Arvanitaki A (1942) Effects evoked in an axon by the activity of a contiguos one. J Neurophysiol 5:89–108
Augustine GJ (2001) How does calcium trigger neurotransmitter release? Curr Opin Neurobiol 11(3):320–326
Bair W, Koch C (1996) Temporal precision of spike trains in extrastriate cortex of the behaving macaque monkey. Neural Comput 8(6):1185–202
Blair E, Erlanger J (1933) A comparison of the characteristics of axons through their individual electric responses. Am J Physiol 106:524–564
Braitenberg V, Schütz A (1998) Cortex: statistics and geometry of neuronal connectivity, 2nd edn. Springer, Hamburg
Bryant H, Segundo J (1976) Spike initiation by transmembrane current: a white-noise analysis. J Physiol (London) 260:279–314
Chow C, White J (1996) Spontaneous action potentials due to channel fluctuations. Biophys J 71:3012–3021
Clay JR, DeFelice LJ (1983) Relationship between membrane excitability and single channel open–close kinetics. Biophys J 42(2):151–157
Conti F, Wanke E (1975) Channel noise in nerve membranes and lipid bilayers. Q Rev Biophys 8:451–506
Cover T, Thomas J (1991) Elements of information theory, 1st edn. Wiley series in telecommunications. Wiley-Interscience, New York
Debanne D (2004) Information processing in the axon. Nat Rev Neurosci 5(4):304–16
de Polavieja G, Harsch A, Kleppe I, Robinson H, Juusola M (2005) Stimulus history reliably shapes action potential waveforms of cortical neurons. J Neurosci 25(23):5657–5665
Derksen H, Verveen A (1966) Fluctuations of resting neural membrane potential. Science 12:1388–1389
Dorval A Jr, White J (2005) Channel noise is essential for perithreshold oscillations in entorhinal stellate neurons. J Neurosci 25(43):10025–10028
Faisal AA (2007) Studying channelopathies at the functional level using a system identification approach. In: Siebes APJM, Berthold MR, Glen RC, Feelders AJ (eds) Computational lifesciences II, vol 940. AIP, pp 113–126
Faisal AA (2010) Stochastic methods in neuroscience.Chapter 11:Stochastic simulations of neurons, axons, and action potentials. Oxford University Press, Oxford, pp 297–343
Faisal A, Laughlin S (2004) Effect of channel noise on the propagating ap wave form and its potential impact on synaptic transmission. J Physiol 555P:492
Faisal A, Laughlin S (2007) Stochastic simulations on the reliability of action potential propagation in thin axons. PLoS Comput Biol 3(5):e79
Faisal AA, Niven JE (2006) A simple method to simultaneously track the numbers of expressed channel proteins in a neuron. Lect Notes Comput Sci 4216:257
Faisal A, Laughlin S, White J (2002) How reliable is the connectivity in cortical neural networks? In: Wunsch D (ed) Proceedings of the IEEE international joint conference on neural networks 2002, Honolulu. INNS, pp 1661–1667
Faisal A, White J, Laughlin S (2005) Ion-channel noise places limits on the miniaturization of the brain’s wiring. Curr Biol 15(12):1143–1149
Faisal A, Selen L, Wolpert D (2008) Noise in the nervous system. Nat Rev Neurosci 9(4):292–303
Fitzhugh R (1965) A kinetic model of the conductance changes in nerve membrane. J Cell Comp Physiol 66:111–118
Franciolini F (1987) Spontaneous firing and myelination of very small axons. J theor Biol 128:127–134
Frankenhaeuser B, Hodgkin A (1956) The after-effects of impulses in the giant nerve fibers of loligo. J Physiol 131:341–376
Franks KM, Stevens CF, Sejnowski TJ (2003) Independent sources of quantal variability at single glutamatergic synapses. J Neurosci 23(8):3186–95
Hartwell L, Hopfield J, Leibler S, Murray A (1999) From molecular to modular cell biology. Nature 402 Supplement:C47–C42
Hille B (1970) Ionic channels in nerve membranes. Prog. Biophys. Mol. Biol 21:3–28
Hille B (2001) Ion channels of excitable membranes, 3rd edn. Sinauer Associates, Sunderland, p 814
Ho N, Destexhe A (2000) Synaptic background activity enhances the responsiveness of neocortical pyramidal neurons. J Neurophysiol 84(3):1488–96
Hodgkin A (1964) The ionic basis of nervous conduction. Science 145(3637):1148–1154
Hodgkin A, Huxley A (1952) Quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol (London) 117:500–544
Horikawa Y (1991) Noise effects on spike propagation in the stochastic Hodgkin–Huxley models. Biol Cybern 66:19–25
Katz B (1971) Quantal mechanism of neural transmitter release. Science 173(992):123–126
Katz B, Schmitt O (1940) Electric interaction between two adjacent nerve fibres. J.Physiol 97:471–488
Koch C (1999) Biophysics of computation. Computational neuroscience. Oxford University Press, Oxford
Lass Y, Abeles M (1975a) Transmission of information by the axon: 1. Noise and memory in the myelinated nerve fiber of the frog. Biol Cybern 19:61–67
Lass Y, Abeles M (1975b) Transmission of information by the axon: 2. Information theoretic analysis(?). Biol Cybern 19:121–125
Laughlin S (1981) A simple coding procedure enhances a neuron’s information capacity. Z Naturforsch 36c:910–912
Lecar H, Nossal R (1971) Theory of threshold fluctuations in nerves: 2. Analysis of various sources of membrane noise. Biophys J 11:1068–1084
Mainen ZF, Joerges J, Huguenard JR, Sejnowski TJ (1995) A model of spike initiation in neocortical pyramidal neurons. Neuron 15(6):1427–39
Manwani A, Koch C (1999a) Detecting and estimating signals in noisy cable structures, i: neuronal noise sources. Neural Comput 11:1797–1829
Manwani A, Koch C (1999b) Detecting and estimating signals in noisy cable structures, ii: information theoretic analysis. Neural Comput 11:11831–1873
Markov A (1906) Rasprostranenie zakona bol’shih chisel na velichiny, zavisyaschie drug ot druga. Izvestiya Fiziko-matematicheskogo obschestva pri Kazanskom universitete 15(2-ya seriya):135–156
Markov A (1971) Extension of the limit theorems of probability theory to a sum of variables connected in a chain (translation). In: Howard R (ed) Dynamic probabilistic systems, vol 1: Markov Chains. Wiley, New York. Reprinted in Appendix B
McBain C, Traynelis S, Dingledine R (1990) Regional variation of extracellular space in the hippocampus. Science 249:674–677
Nicholson C, Phillips JM (1981) Ion diffusion modified by tortuosity and volume fraction in the extracellular microenvironment of the rat cerebellum. J Physiol 321:225–57
Patlak J (1991) Molecular kinetics of voltage-dependent na+ channels. Physiol Rev 71(4):1047–1080
Pecher C (1939) La fluctuation d’excitabilite de la fibre nerveuse. Arch Int Physiol Biochem 49:129–152
Prinz AA, Abbott LF, Marder E (2004a) The dynamic clamp comes of age. Trends Neurosci 27(4):218–224
Prinz AA, Bucher D, Marder E (2004b) Similar network activity from disparate circuit parameters. Nat Neurosci 7(12):1345–1352
Rall W (1969a) Distributions of potential in cylindrical coordinates and time constants for a membrane cylinder. Biophys J 9(12):1509–41
Rall W (1969b) Time constants and electrotonic length of membrane cylinders and neurons. Biophys J 9(12):1483–508
Rieke F, Warland D, de Ruyter van Steveninck RR, Bialek W (1997) Spikes : exploring the neural code. Computational neuroscience. MIT Press, Cambridge
Robinson H, Kawai N (1993) Injection of digitally synthesized synaptic conductance transients to measure the integrative properties of neurons. J Neurosci Methods 49(3):157–165
Rubinstein J.T (1995) Threshold fluctuations in an n sodium channel model of the node of ranvier. Biophys J 68(3):779–85
Sakmann B, Neher E (1995) Single-Channel recording, 2nd edn. Plenum Press, New York
Schmitz D et al (2001) Axo-axonal coupling: a novel mechanism for ultrafast neuronal communication. Neuron 31:831–840
Schneidman E, Freedman B, Segev I (1998) Ion channel stochasticity may be critical in determining the reliability and precision of spike timing. Neural Comput 10:1679–1703
Shadlen MN, Newsome WT (1995) Is there a signal in the noise? Curr Opin Neurobiol 5(2): 248–50
Shadlen MN, Newsome WT (1998) The variable discharge of cortical neurons: implications for connectivity, computation, and information coding. J Neurosci 18(10):3870–96
Shannon C (1948) A mathematical theory of communication. Bell Syst Tech J 27:373–423,623–656
Sharp A, O’Neil M, Abbott L, Marder E (1993) Dynamic clamp: computer-generated conductances in real neurons. J Neurophysiol 69(3):992–995
Sigworth FJ (1980) The variance of sodium current fluctuations at the node of ranvier. J Physiol 307:97–129
Sigworth FJ, Neher E (1980) Single na+ channel currents observed in cultured rat muscle cells. Nature 287(5781):447–449
Skaugen E, WallœL (1979) Firing behaviour in a stochastic nerve membrane model based upon the Hodgkin–Huxley equations. Acta Physiol Scand 107:343–363
Softky WR, Koch C (1993) The highly irregular firing of cortical cells is inconsistent with temporal integration of random epsps. J Neurosci 13(1):334–50
Steinmetz PN, Manwani A, Koch C, London M, Segev I (2000) Subthreshold voltage noise due to channel fluctuations in active neuronal membranes. J Comput Neurosci 9(2):133–48
Strassberg A, DeFelice L (1993) Limitation of the Hodgkin–Huxley formalism: effects of single channel kinetics on transmembrane voltage dynamics. Nueral Comput 5:843–855
Strong S, Koberle R, de Ruyter van Steveninck R, Bialek W (1998) Entropy and information in neural spike trains. Phys Rev Lett 80(1):197–200
Tamas G, Szabadics J (2004) Summation of unitary ipsps elicited by identified axo-axonic interneurons. Cereb Cortex 14(8):823–826
Verveen AA (1962) Axon diameter and fluctuation in excitability. Acta Morphol Neerl Scand 5:79–85
Verveen AA, Derksen HE, Schick KL (1967) Voltage fluctuations of neural membrane. Nature 216(115):588–589
Waxman SG, Bennett MV (1972) Relative conduction velocities of small myelinated and non-myelinated fibres in the central nervous system. Nat New Biol 238(85):217–219
White J, Rubinstein J, Kay A (2000) Channel noise in neurons. Trends Neurosci 23(3):131–137
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Faisal, A.A. (2012). Noise in Neurons and Other Constraints. In: Le Novère, N. (eds) Computational Systems Neurobiology. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-3858-4_8
Download citation
DOI: https://doi.org/10.1007/978-94-007-3858-4_8
Published:
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-007-3857-7
Online ISBN: 978-94-007-3858-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)