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Published October 27, 2004 | Published
Journal Article Open

Intrinsic Noise in Cultured Hippocampal Neurons: Experiment and Modeling

Abstract

Ion channels open and close stochastically. The fluctuation of these channels represents an intrinsic source of noise that affects the input-output properties of the neuron. We combined whole-cell measurements with biophysical modeling to characterize the intrinsic stochastic and electrical properties of single neurons as observed at the soma. We measured current and voltage noise in 18 d postembryonic cultured neurons from the rat hippocampus, at various subthreshold and near-threshold holding potentials in the presence of synaptic blockers. The observed current noise increased with depolarization, as ion channels were activated, and its spectrum demonstrated generalized 1/fbehavior. Exposure to TTX removed a significant contribution from Na^+ channels to the noise spectrum, particularly at depolarized potentials, and the resulting spectrum was now dominated by a single Lorentzian (1/f^2) component. By replacing the intracellular K^+ with Cs^+, we demonstrated that a major portion of the observed noise was attributable to K^+ channels. We compared the measured power spectral densities to a 1-D cable model of channel fluctuations based on Markov kinetics. We found that a somatic compartment, in combination with a single equivalent cylinder, described the effective geometry from the viewpoint of the soma. Four distinct channel populations were distributed in the membrane and modeled as Lorentzian current noise sources. Using the NEURON simulation program, we summed up the contributions from the spatially distributed current noise sources and calculated the total voltage and current noise. Our quantitative model reproduces important voltage- and frequency-dependent features of the data, accounting for the 1/f behavior, as well as the effects of various blockers.

Additional Information

©2004 Society for Neuroscience. Received March 15, 2004. Revision received August 12, 2004. Accepted August 13, 2004. This work was supported by the National Institute of Mental Health, the National Science Foundation, and a Sloan-Swartz Postdoctoral Fellowship to K.D. We are deeply indebted to Irina Sokolova and Sheri McKinney for help with the culture preparation and patch clamp. Additionally,wethank Eric Slimko, Sacha Malin, Gilad Jacobson, Yosef Yarom, and Idan Segev for valuable discussions and Michael Hines and Ted Carnevale for assistance with the NEURON simulation environment.

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