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Reduction of spike afterdepolarization by increased leak conductance alters interspike interval variability.

ABSTRACT: Data from neurons in vivo have shown that spike output can often sustain episodes of high variability. Theoretical studies have indicated that the high conductance state of neurons brought on by synaptic activity can contribute to an increase in the variability of spike output by decreasing the integration timescale of the neuron. In the present work, we were interested in understanding how background synaptic conductance activity alters the interspike interval (ISI) variability of layer III pyramidal cells of the medial entorhinal cortex. We compared ISI variability in pyramidal cells as a result of synaptic current- or conductance-mediated membrane fluctuations. We found that the effects of background synaptic conductance activity on ISI variability depend on the neuron type. In pyramidal cells lacking spike frequency adaptation, the variability increased in relation to a comparable synaptic current stimulus. In contrast, in pyramidal cells displaying spike frequency adaptation, the synaptic conductance stimulus produced lower ISI variability. To understand this result, we constructed a phenomenological model that reproduced the basic properties of these neurons under control and increased leak conductance. We found that leak can change the properties of the neuron by acting as a bifurcation parameter that reduces the afterdepolarization (ADP) and decreases the slope (gain) of the frequency-current relationship, particularly for transient stimuli. A lower gain with the added leak causes a reduction in ISI variability. We conclude that the ability of a high conductance state to increase ISI variability cannot be generalized and can depend on the spike ADP dynamics expressed by the neuron.

SUBMITTER: Fernandez FR

PROVIDER: S-EPMC2723775 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

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Reduction of spike afterdepolarization by increased leak conductance alters interspike interval variability.

Fernandez Fernando R FR White John A JA

The Journal of neuroscience : the official journal of the Society for Neuroscience 20090101 4

Data from neurons in vivo have shown that spike output can often sustain episodes of high variability. Theoretical studies have indicated that the high conductance state of neurons brought on by synaptic activity can contribute to an increase in the variability of spike output by decreasing the integration timescale of the neuron. In the present work, we were interested in understanding how background synaptic conductance activity alters the interspike interval (ISI) variability of layer III pyr ...[more]

PMID: 19176806

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Project description:The generation of neural action potentials (spikes) is random but nevertheless may result in a rich statistical structure of the spike sequence. In particular, contrary to the popular renewal assumption of theoreticians, the intervals between adjacent spikes are often correlated. Experimentally, different patterns of interspike-interval correlations have been observed and computational studies have identified spike-frequency adaptation and correlated noise as the two main mechanisms that can lead to such correlations. Analytical studies have focused on the single cases of either correlated (colored) noise or adaptation currents in combination with uncorrelated (white) noise. For low-pass filtered noise or adaptation, the serial correlation coefficient can be approximated as a single geometric sequence of the lag between the intervals, providing an explanation for some of the experimentally observed patterns. Here we address the problem of interval correlations for a widely used class of models, multidimensional integrate-and-fire neurons subject to a combination of colored and white noise sources and a spike-triggered adaptation current. Assuming weak noise, we derive a simple formula for the serial correlation coefficient, a sum of two geometric sequences, which accounts for a large class of correlation patterns. The theory is confirmed by means of numerical simulations in a number of special cases including the leaky, quadratic, and generalized integrate-and-fire models with colored noise and spike-frequency adaptation. Furthermore we study the case in which the adaptation current and the colored noise share the same time scale, corresponding to a slow stochastic population of adaptation channels; we demonstrate that our theory can account for a nonmonotonic dependence of the correlation coefficient on the channel's time scale. Another application of the theory is a neuron driven by network-noise-like fluctuations (green noise). We also discuss the range of validity of our weak-noise theory and show that by changing the relative strength of white and colored noise sources, we can change the sign of the correlation coefficient. Finally, we apply our theory to a conductance-based model which demonstrates its broad applicability.

Project description:Cardiovascular diseases, including ventricular arrhythmias are responsible for increased mortality in patients with acromegaly. Acromegaly may cause repolarization abnormalities such as QT prolongation and impairment of repolarization reserve enhancing liability to arrhythmia. The aim of this study was to determine the short-term beat-to-beat QT variability in patients with acromegaly. Thirty acromegalic patients (23 women and 7 men, mean age±SD: 55.7±10.4 years) were compared with age- and sex-matched volunteers (mean age 51.3±7.6 years). Cardiac repolarization parameters including frequency corrected QT interval, PQ and QRS intervals, duration of terminal part of T waves (Tpeak-Tend) and short-term variability of QT interval were evaluated. All acromegalic patients and controls underwent transthoracic echocardiographic examination. Autonomic function was assessed by means of five standard cardiovascular reflex tests. Comparison of the two groups revealed no significant differences in the conventional ECG parameters of repolarization (QT: 401.1±30.6 ms vs 389.3±16.5 ms, corrected QT interval: 430.1±18.6 ms vs 425.6±17.3 ms, QT dispersion: 38.2±13.2 ms vs 36.6±10.2 ms; acromegaly vs control, respectively). However, short-term beat-to-beat QT variability was significantly increased in acromegalic patients (4.23±1.03 ms vs 3.02±0.80, P<0.0001). There were significant differences between the two groups in the echocardiographic dimensions (left ventricular end diastolic diameter: 52.6±5.4 mm vs 48.0±3.9 mm, left ventricular end systolic diameter: 32.3±5.2 mm vs 29.1±4.4 mm, interventricular septum: 11.1±2.2 mm vs 8.8±0.7 mm, posterior wall of left ventricle: 10.8±1.4 mm vs 8.9±0.7 mm, P<0.05, respectively). Short-term beat-to-beat QT variability was elevated in patients with acromegaly in spite of unchanged conventional parameters of ventricular repolarization. This enhanced temporal QT variability may be an early indicator of increased liability to arrhythmia.

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Reduction of spike afterdepolarization by increased leak conductance alters interspike interval variability.

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Reduction of spike afterdepolarization by increased leak conductance alters interspike interval variability.

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