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Cholinergic receptor subtypes and their role in cognition, emotion, and vigilance control: An overview of preclinical and clinical findings

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Abstract

Rationale

The cholinergic system has long been linked to cognitive processes. Two main classes of acetylcholine (ACh) receptors exist in the human brain, namely muscarinic and nicotinic receptors, of which several subtypes occur.

Objectives

This review seeks to provide an overview of previous findings on the influence of cholinergic receptor manipulations on cognition in animals and humans, with particular emphasis on the role of selected cholinergic receptor subtypes. Furthermore, the involvement of these receptor subtypes in the regulation of emotion and brain electrical activity as measured by electroencephalography (EEG) shall be addressed since these domains are considered to be important modulators of cognitive functioning.

Results

In regard to cognition, the muscarinic receptor subtypes have been implicated mainly in memory functions, but have also been linked to attentional processes. The nicotinic α7 receptor subtype is involved in working memory, whereas the α4β2* subtype has been linked to tests of attention. Both muscarinic and nicotinic cholinergic mechanisms play a role in modulating brain electrical activity. Nicotinic receptors have been strongly associated with the modulation of depression and anxiety.

Conclusions

Cholinergic receptor manipulations have an effect on cognition, emotion, and brain electrical activity as measured by EEG. Changes in cognition can result from direct cholinergic receptor manipulation or from cholinergically induced changes in vigilance or affective state.

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Abbreviations

5-CSRT:

Five-choice serial reaction time

ACh:

Acetylcholine

CPT:

Continuous performance task

EEG:

Electroencephalography

FDG:

Fluoro-2-deoxy-d-glucose

HVS:

High-voltage spindle

mAChR:

Muscarinic acetylcholine receptor

MPTP:

Methylphenyltetrahydropyridin

nAChR:

Nicotinic acetylcholine receptor

PET:

Positron emission tomography

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Authors and Affiliations

  1. Department of Psychiatry, University of Leipzig, Semmelweisstr. 10, 04103, Leipzig, Germany

    Susanne Graef, Peter Schönknecht & Ulrich Hegerl

  2. Department of Nuclear Medicine, University of Leipzig, Liebigstr. 18, 04103, Leipzig, Germany

    Osama Sabri

  3. Max Planck Institute for Human Cognitive and Brain Sciences, Stephanstr. 1a, 04103, Leipzig, Germany

    Susanne Graef

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  1. Susanne Graef
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  2. Peter Schönknecht
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  3. Osama Sabri
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  4. Ulrich Hegerl
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Correspondence to Susanne Graef.

Additional information

The asterisk used in the receptor nomenclature indicates that the receptor complex may contain additional subunits.

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Graef, S., Schönknecht, P., Sabri, O. et al. Cholinergic receptor subtypes and their role in cognition, emotion, and vigilance control: An overview of preclinical and clinical findings. Psychopharmacology 215, 205–229 (2011). https://doi.org/10.1007/s00213-010-2153-8

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