Review
INMED/TINS special issue
Are corticothalamic ‘up’ states fragments of wakefulness?

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The slow (<1 Hz) oscillation, with its alternating ‘up’ and ‘down’ states in individual neurons, is a defining feature of the electroencephalogram (EEG) during slow-wave sleep (SWS). Although this oscillation is well preserved across mammalian species, its physiological role is unclear. Electrophysiological and computational evidence from the cortex and thalamus now indicates that slow-oscillation ‘up’ states and the ‘activated’ state of wakefulness are remarkably similar dynamic entities. This is consistent with behavioural experiments suggesting that slow-oscillation ‘up’ states provide a context for the replay, and possible consolidation, of previous experience. In this scenario, the T-type Ca2+ channel-dependent bursts of action potentials that initiate each ‘up’ state in thalamocortical (TC) neurons might function as triggers for synaptic and cellular plasticity in corticothalamic networks. This review is part of the INMED/TINS special issue Physiogenic and pathogenic oscillations: the beauty and the beast, based on presentations at the annual INMED/TINS symposium (http://inmednet.com).

Introduction

The function of sleep is a mystery that has long fascinated biologists and is still the matter of intense debate [1]. One of the most prominent features of sleep in mammals is the occurrence of the slow (<1 Hz) sleep oscillation that dominates slow-wave sleep (SWS; Box 1). This oscillation is extremely similar in different species 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, suggesting that it might have well-defined, conserved roles. Fairly recently, behavioural experiments have indicated that SWS might be related to memory consolidation 11, 12, 13, 14, 15, 16, 17 and the basis of such consolidation might be the slow sleep oscillation itself 12, 14, 15, 16, 17, 18. Here, we explore this issue from an electrophysiological and computational modelling perspective. Specifically, we reassess various electrophysiological measurements of the waking (or wake-like) state and compare them with those obtained for the ‘up’ state of the slow (<1 Hz) sleep oscillation in the specific brain structures involved in its generation. The extremely close similarity of both single-neuron and network dynamics during these different scenarios is compatible with the results of behavioural experiments indicating that during SWS selected epochs of prior experience are episodically replayed and consolidated.

Section snippets

The dynamics of single neurons during ‘activated’ states and slow-wave sleep

We start by reviewing the essential cellular correlates of the ‘activated’ brain state, which corresponds to attentive wakefulness, and examine how they qualitatively compare with those of SWS. Brain activation is invariably associated with a so-called ‘desynchronized’ electroencephalogram (EEG), which consists of low-amplitude fluctuations at relatively high frequencies (>15 Hz) 5, 6 (Figure 1a). This state is associated with tonic and irregular firing of cortical neurons [19], the membrane

Similarities in cortical network dynamics between the ‘activated’ state and ‘up’ states of the slow oscillation

The similarity between activated states and the slow-oscillation ‘up’ state in the cortex is not only apparent at the rank of single cells, but can also be found at the level of the EEG and local field potentials (LFPs) (see Glossary). First, the typical desynchronized EEG pattern of arousal is evident locally in the EEG during ‘up’ states, both in the naturally sleeping animal (Figure 1a) and during anaesthesia (Figure 1b). A second, and stronger, indication of the similarities comes from

Similarities between a persistently depolarized state and the ‘up’ state of the slow oscillation in thalamocortical and thalamic reticular nucleus neurons

Both cortical and thalamic slow (<1 Hz) oscillations can be reproduced using in vitro models. In cortical slices, the slow oscillation is reliant on a modified, artificial cerebrospinal fluid, containing a reduced Ca2+ concentration, and is generated primarily by network-dependent mechanisms 24, 42 (see Glossary). In thalamic slices, by contrast, the slow oscillation in both TC and TRN neurons is generated mainly by intrinsic mechanisms 9, 43, 44, 45, 46 (see Glossary). These oscillations have

Slow-oscillation ‘up’ states as micro-wake ‘fragments’

An assortment of data from the corticothalamic system has been presented that converges to establish that, at both single-cell and neuronal-network levels, the fully activated brain state and slow-oscillation ‘up’ states are dynamically similar. An attractive interpretation of this is that individual corticothalamic ‘up’ states provide micro-wake-like contexts that facilitate specific types of neuronal interaction. In particular, they might provide brief epochs of network dynamics that aid the

T-type Ca2+ channel-mediated bursts in thalamocortical neurons as a trigger for ‘up’ states and synaptic plasticity

If individual ‘up’ states contain segments of prior wake-related dynamics, an attractive hypothesis is that these segments are determined and selected during wakefulness through ongoing remodelling of cortical [59] or corticothalamic attractors by sensory input [18]. Such attractors might then be preferentially activated in sleep during the slow-oscillation ‘up’ state [18], particularly in response to a strong thalamic signal, which is a highly effective way to trigger internally defined

Concluding remarks

Electrophysiological and modelling data show that ‘up’ states of the slow (<1 Hz) sleep oscillation are dynamically equivalent to the activated state of wakefulness. This is in agreement with several behavioural investigations, which indicate that waking activities are replayed, and possibly consolidated, during SWS. The prominent T-type Ca2+ channel-mediated bursts in TC neurons might function as key network triggers that ensure the synchronous start of slow-oscillation ‘up’ states across

Acknowledgements

This review is dedicated to the memory of Mircea Steriade. Work in our laboratories is supported by The Wellcome Trust (grants 71436, 78311 and 78403 to V.C. and S.W.H. and the CNRS, Human Frontier Science Program and European Community (A.D. and M.R.). Additional information regarding other published work from our laboratories is available at http://www.thalamus.org.uk and http://cns.iaf.cnrs-gif.fr.

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