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The high-conductance state of neocortical neurons in vivo

Nature Reviews Neuroscience volume 4, pages 739–751 (2003)Cite this article

A Correction to this article was published on 01 December 2003

Key Points

  • Neocortical neurons in vivo are subjected to intense synaptic bombardment, leading to a 'high-conductance state' that differs markedly from the conditions measured in cortical slices in vitro.

  • During barbiturate anaesthesia, as well as in slices, neuronal activity is greatly reduced compared with states of activated or desynchronized electroencephalogram (EEG) activity, such as in awake animals. During EEG-activated states, intracellular recordings show a depolarized and fluctuating membrane potential, a low input resistance and high levels of spontaneous firing. In slices, cells have a high input resistance, are hyperpolarized and show little spontaneous activity.

  • Active dendritic properties such as the ability to generate and propagate action potentials have important implications for the integration of synaptic inputs. Computational models have been used to investigate these implications for in vivo processing.

  • These models predict the following 'computational principles' for high-conductance states: enhanced responsiveness and gain modulation; equalization of synaptic efficacies; increased temporal resolution; and probabilistic and irregular behaviour. By virtue of these principles, cortical neurons would be tuned to optimally track fine temporal variations in their synaptic inputs despite their stochastic nature.

  • In dynamic-clamp experiments, in vitro electrophysiology is combined with computational modelling to 'recreate' the characteristics of high-conductance states in cortical slices, allowing the effects of the high-conductance state on neuronal responsiveness to be measured directly.

  • Such experiments confirm that synaptic noise enhances neuronal responsiveness and modulates the gain of neurons. They could also be used to test the predictions that it equalizes synaptic efficacies, increases temporal resolution and induces probabilistic behaviour.

Abstract

Intracellular recordings in vivo have shown that neocortical neurons are subjected to an intense synaptic bombardment in intact networks and are in a 'high-conductance' state. In vitro studies have shed light on the complex interplay between the active properties of dendrites and how they convey discrete synaptic inputs to the soma. Computational models have attempted to tie these results together and predicted that high-conductance states profoundly alter the integrative properties of cortical neurons, providing them with a number of computational advantages. Here, we summarize results from these different approaches, with the aim of understanding the integrative properties of neocortical neurons in the intact brain.

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Figure 1: Intracellular and electroencephalogram (EEG) recordings during different states of activity.
Figure 2: Conductance measurements during different states of activity.
Figure 3: Dendritic excitability.
Figure 4: Enhanced responsiveness during high-conductance states.
Figure 5: Equalization of synaptic efficacies during high-conductance states.
Figure 6: Sharper temporal resolution during high-conductance states.
Figure 7: Dynamic-clamp experiments in vitro reproduce in vivo high-conductance states.

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Acknowledgements

We thank M. Badoual, T. Bal, M. Steriade and I. Timofeev for intracellular recording data. Research supported by the Centre National de la Recherche Scientifique (France), Future and Emerging Technologies (European Union), the Human Frontier Science Program and the National Institutes of Health.

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Authors and Affiliations

  1. Integrative and Computational Neuroscience Unit (UNIC), CNRS, 1 Avenue de la Terrasse, Gif-sur-Yvette, 91198, France

    Alain Destexhe & Michael Rudolph

  2. Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, 07102, New Jersey, USA

    Denis Paré

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  1. Alain Destexhe
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  2. Michael Rudolph
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  3. Denis Paré
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Correspondence to Alain Destexhe.

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FURTHER INFORMATION

Laboratory for Computational Neuroscience

Glossary

INPUT RESISTANCE

The voltage change elicited by the injection of current into a cell, divided by the amount of current injected.

LEAK CONDUCTANCE

A constitutively active conductance, the reversal potential of which is called the leak reversal.

DELAYED RECTIFIER K+ CHANNELS

Channels commonly found in axons, the conductance of which changes with a delay after a voltage step. They are important for the generation of action potential bursts, the regulation of pacemaker potentials and other functions.

A-TYPE K+ CHANNELS

This type of channel activates and inactivates very rapidly in response to voltage changes, preventing neurons from responding to fast depolarizations.

TEMPORAL SUMMATION

The way in which non-simultaneous synaptic events add in time. One of the basic elements of synaptic integration.

POWER SPECTRUM

After analysing a waveform with a Fourier transform, its amplitude spectrum is the collection of amplitudes of the sinusoidal components that result from the analysis. The power spectrum is the square of the amplitude spectrum.

COLOURED NOISE

White noise is a signal that covers the entire range of component sound frequencies with equal intensity. In coloured noise, the signal covers a narrow band of frequencies.

INTEGRATE-AND-FIRE MODEL

The simplest model of a spiking neuron that takes into account the dynamics of the synaptic inputs.

STOCHASTIC RESONANCE

The facilitated or optimized response of a non-linear dynamical system to stimuli in the presence of non-vanishing noise, usually expressed as a peak of the signal-to-noise ratio.

CABLE THEORY

Mathematical description of the purely passive spread of electrical current in a nerve fibre. It is conceptually similar to the theory that is needed to understand the properties of long cables.

MEMBRANE TIME CONSTANT

A quantity that depends on the capacitance and resistance of the cell membrane, and which sets a timescale for changes in voltage. A small time constant means that the membrane potential can change rapidly.

SHUNTING INHIBITION

A phenomenon whereby membrane depolarization that is induced by a given current is attenuated because of an enhanced membrane conductance.

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Destexhe, A., Rudolph, M. & Paré, D. The high-conductance state of neocortical neurons in vivo. Nat Rev Neurosci 4, 739–751 (2003). https://doi.org/10.1038/nrn1198

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