×

A new analytical method of studying post-synaptic currents. (English) Zbl 0943.92012

Summary: A powerful methodology for analyzing post-synaptic currents recorded trom central neurons is presented. An unknown quantity of transmitter molecules released from presynaptic terminals by electrical stimulation of nerve fibers generates a post-synaptic response at the synaptic site. The current induced at the synaptic junction is assumed to rise rapidly and decay slowly with its peak amplitude being proportional to the number of released transmitter molecules. The signal so generated is then distorted by the cable properties of the dendrite, modeled as a time-invariant, linear filter with unknown parameters. The response recorded from the cell body of the neuron following the electrical stimulation is contaminated by zero-mean, white, Gaussian noise. The parameters of the signal are then evaluated from the observation sequence using a quasi-profile likelihood estimation procedure. These parameter values are then employed to deconvolve each measured post-synaptic response to produce an optimal estimate of the transmembrane current flux. From these estimates we derive the amplitude of the synaptic current and the relative amount of transmitter molecules that elicited each response. The underlying amplitude fluctuations in the entire data sequence are investigated using a non-parametric technique based on kernel smoothing procedures. The effectiveness of the new methodology is illustrated in various simulation examples.

MSC:

92C20 Neural biology
62P10 Applications of statistics to biology and medical sciences; meta analysis
PDFBibTeX XMLCite
Full Text: DOI

References:

[1] del Castillo, J.; Katz, B., Quantal components of the end-plate potential, J. Physiol., 124, 560 (1954)
[2] Boyd, I. A.; Martin, A. R., The end-plate potential in mammalian muscle, J. Physiol., 132, 74 (1956)
[3] Jack, J. J.B.; Redman, S. J.; Wong, K., The components of synaptic potentials evoked in cat spinal motoneurones by impulses in single group Ia afferents, J. Physiol., 321, 65 (1981)
[4] Sayer, R. J.; Redman, S. J.; Andersen, P., Amplitude fluctuations in small EPSPs recorded from CA1 pyramidal cells in the guinea pig hippocampal slice, J. Neurosci., 9, 840 (1989)
[5] Sayer, R. J.; Friedlander, M. J.; Redman, S. J., The time course and amplitude of EPSPs evoked at synapses between pairs of CA3/CA1 neurons in the hippocampal slice, J. Neurosci., 10, 826 (1990)
[6] Stricker, C.; Redman, S., Statistical models of synaptic transmission evaluated using the expectation-maximization algorithm, Biophys. J., 656 (1994)
[7] Stricker, C.; Redman, S.; Daley, D., Statistical analysis of synaptic transmission: model discrimination and confidence limit, Biophys. J., 67, 532 (1994)
[8] Liao, D.; Jones, A.; Malinow, R., Direct measurement of quantal changes underlying long-term potentiation in CA1 hippocampus, Neuron., 9, 1089 (1992)
[9] Bliss, T. V.P.; Collingridge, G. L., A synaptic model of memory: long-term potentiation in the hippocampus, Nature, 361, 31 (1993)
[10] Uteshev, V. V.; Pennefather, P. S., Analytical description of the activation of multi-state receptors by continuous neurotransmitter signal at brain synapses, Biophys. J., 72, 1127 (1997)
[11] Wahl, L. M.; Jack, J. B.; Larkman, A. U.; Stratford, K. J., The effects of synaptic noise on measurements of evoked excitatory synaptic response amplitude, Biophys. J., 73, 205 (1997)
[12] Yuste, R.; Denk, W., Dendritic spines as basic functional units of neuronal integration, Nature, 375, 628 (1995)
[13] Magee, J.; Hoffman, D.; Colbert, C.; Johnston, D., Electrical and calcium signaling in dendrites of hippocampal pyramidal neurons, Ann. Rev. Physiol., 60, 327 (1998)
[14] Poskitt, D. S.; Doğançay, K.; Chung, S. H., Double blind deconvolution: the analysis of post-synaptic currents in nerve cells, J. Roy. Statist. Soc., 61, 191 (1999) · Zbl 0927.92010
[15] Bard, Y., Nonlinear Parameter Estimation (1974), Academic Press: Academic Press New York · Zbl 0345.62045
[16] Silverman, B. W., Density Estimation for Statistical Data Analysis (1986), Chapman and Hall: Chapman and Hall London · Zbl 0617.62042
[17] Wand, M. P.; Jones, M. C., Kernel Smoothing (1995), Chapman and Hall: Chapman and Hall London · Zbl 0854.62043
[18] Chu, C. K.; Chung, P. E., Estimation of jump points and jump values of a density function, Statistica Sinica, 6, 75 (1996) · Zbl 0839.62039
[19] Efron, B.; Tibshirani, R., An Introduction to the Bootstrap (1993), Chapman and Hall: Chapman and Hall New York · Zbl 0835.62038
[20] Stricker, C.; Field, A. C.; Redman, S. J., Statistical analysis of amplitude fluctuations in EPSCs evoked in rat CA1 pyramidal neurons in vitro, J. Physiol., 490, 419 (1996)
[21] Stricker, C.; Field, A. C.; Redman, S. J., Changes in quantal parameters of EPSPs in rat CA1 neurones in vitro after the induction of long-term potentiation, J. Physiol., 490, 443 (1996)
[22] McLachlan, E. M., The statistics of transmitter release at chemical synapses, Int. Rev. Physiol. Neurophysiol. III, 17, 49 (1978)
[23] J.M. Bekkers, G.G. Richerson, C.F. Stevens, Origin of variability in quantal size in cultured hippocampal neurons and hippocampal slices, Proc. Nat. Acad. Sci. U.S.A. 87 (1990) 5359; J.M. Bekkers, G.G. Richerson, C.F. Stevens, Origin of variability in quantal size in cultured hippocampal neurons and hippocampal slices, Proc. Nat. Acad. Sci. U.S.A. 87 (1990) 5359
[24] Bekkers, J. M., Quantal analysis of synaptic transmission in the central nervous system, Current Opinions in Neurobiol., 4, 360 (1994)
[25] Bekkers, J. M.; Stevens, C. F., Quantal analysis of EPSCs recorded from small numbers of synapses in hippocampal cultures, J. Neurophysiol., 73, 1145 (1995)
[26] J.D. Clements, Quantal synaptic transmission? Nature 353 (1991) 396; J.D. Clements, Quantal synaptic transmission? Nature 353 (1991) 396
This reference list is based on information provided by the publisher or from digital mathematics libraries. Its items are heuristically matched to zbMATH identifiers and may contain data conversion errors. In some cases that data have been complemented/enhanced by data from zbMATH Open. This attempts to reflect the references listed in the original paper as accurately as possible without claiming completeness or a perfect matching.