Acetylcholine systems and rhythmic activities during the waking–sleep cycle

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Abstract

The two processes of activation in thalamocortical systems exerted by mesopontine cholinergic neurons are (a) a direct depolarization associated with increased input resistance of thalamic relay neurons, which is antagonized by muscarinic blockers, and (b) a disinhibition of the same neurons via hyperpolarization of inhibitory thalamic reticular neurons. Low-frequency (<15 Hz) oscillations during slow-wave sleep, characterized by rhythmic and prolonged hyperpolarizations, are suppressed by brainstem cholinergic neurons and nucleus basalis cholinergic and GABAergic neurons projecting to thalamic reticular neurons. Fast rhythms (20–60 Hz) appear during the sustained depolarization of thalamic and neocortical neurons during brain-active states that are accompanied by increased release of acetylcholine (ACh) in the thalamus and cerebral cortex. Such fast rhythms also occur during the depolarizing phases of the slow oscillation (0.5–1 Hz) in non-REM sleep. Intracellular recordings of neocortical neurons during natural states of waking and sleep demonstrate stable and increased input resistance of corticocortical and corticothalamic neurons during the sustained depolarization in wakefulness, compared to the depolarizing phase of the slow oscillation in non-REM sleep. Despite the highly increased synaptic inputs along different afferent systems that open many conductances of cortical neurons during wakefulness, the increased input resistance is attributed to the effect of acetylcholine on cortical neurons.

Section snippets

Two cholinergic systems: their connections and related issues

Two cholinergic systems have access to, and activate, thalamocortical and neocortical neurons. One of them originates in the pedunculopontine and laterodorsal tegmental (PPT/LDT) cholinergic nuclei and projects to virtually all thalamic nuclei, but has no direct projections to cortex (see Steriade, 2001b). The other originates in nucleus basalis (NB) and projects to cortex and the thalamic reticular nucleus (reviewed in Asanuma, 1997, Semba, 2000). Both these cholinergic systems exert

From slow-wave sleep oscillatory activities to fast rhythms during brain-active states

Setting brainstem PPT/LDT cholinergic neurons into action results in a blockage of the low-frequency rhythmic activities (<15 Hz) that characterize slow-wave sleep and the occurrence of fast rhythms (∼20–60 Hz) that define waking and REM sleep. These two brain-active states should not be qualified as ‘EEG-desynchronized’, as is often done, because fast rhythms are synchronized over restricted neocortical territories and within corticothalamocortical loops (Steriade et al., 1996a, Steriade et

Relations between brainstem cholinergic and locus coeruleus neurons

Although in brain slices ACh and noradrenaline (NA) act on different cell types via pharmacologically distinct receptors, during natural arousal both PPT and locus coeruleus (LC) nuclei are implicated in rather complex interactions.

In vivo, a comparison between the effects induced by brief pulse-trains to LC and those induced by stimulating PPT cholinergic nucleus with the same parameters showed that, although both stimulated structures blocked the cortically generated slow oscillation, the

Conclusions

  • 1.

    (a) Brainstem cholinergic neurons project to the thalamus, depolarize and increase the apparent input resistance of thalamocortical neurons, and indirectly excite these relay neurons by hyperpolarizing and increasing the membrane conductance of GABAergic thalamic reticular neurons.

  • 2.

    (b) Muscarinic receptor blockers antagonize cortical activation processes elicited by mesopontine reticular neurons. The activation effect elicited by brainstem reticular stimulation is relayed by a glutamatergic

Acknowledgements

Personal experiments reported in this chapter have been supported by grants from the Canadian Institutes for Health Research (MT-3689 and MOP-36545), Natural Sciences and Engineering Research Council of Canada (170538), Human Frontier Science Program (RG0131), and National Institute of Health of United States (NINDS, 1-R01 NS40522-01). I thank the following Ph.D. students and postdoctoral fellows for their skilful and creative collaboration in experiments performed during the past decade (in

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