Elsevier

Behavioural Brain Research

Volume 115, Issue 2, November 2000, Pages 205-218
Behavioural Brain Research

The role of acetylcholine in cortical synaptic plasticity

https://doi.org/10.1016/S0166-4328(00)00259-XGet rights and content

Abstract

This review examines the role of acetylcholine in synaptic plasticity in archi-, paleo- and neocortex. Studies using microiontophoretic application of acetylcholine in vivo and in vitro and electrical stimulation of the basal forebrain have demonstrated that ACh can produce long-lasting increases in neural responsiveness. This evidence comes mainly from models of heterosynaptic facilitation in which acetylcholine produces a strengthening of a second, noncholinergic synaptic input onto the same neuron. The argument that the basal forebrain cholinergic system is essential in some models of plasticity is supported by studies that have selectively lesioned the cholinergic basal forebrain. This review will examine the mechanisms whereby acetylcholine might induce synaptic plasticity. It will also consider the neural circuitry implicated in these studies, namely the pathways that are susceptible to cholinergic plasticity and the neural regulation of the cholinergic system.

Introduction

The present review will consider the role of acetylcholine (ACh) in synaptic plasticity. While this topic has been the subject of several reviews in the last 10 years, (e.g. [40], [121]), the present paper will emphasize the network properties of this modulation. Often confusion arises when data from one level of analysis are assumed to apply to other levels. Consequently, this review will concentrate on synaptic plasticity at the level of single neurons and the pathways involved. Initially, it will discuss the changes produced by iontophoretic application of ACh and the effects of stimulation of the cholinergic cell bodies. The effects of cholinergic lesions on neuronal plasticity will then be discussed followed by a consideration of the pathways that can be facilitated by ACh and how the activity of cholinergic neurons might be controlled by the nervous system. Experiments dealing with the correlation between neural activity and behavioral learning and the effects of cholinergic lesions on behavior are outside the scope of this review (cf. [41], [125], [129], [149]). In this review, the term ‘synaptic plasticity’ will be used in its widest sense to describe changes that influence the communication between two neurons, and will not be restricted to changes in which the synaptic substrate is known. For example, changes in intrinsic membrane properties will be included in this term when they contribute to alterations in the responsiveness of the postsynaptic neuron.

Section snippets

Immediate effects of ACh on electrical activity of neurons

The initial studies on the effects of ACh on cortical neurons used the technique of microiontophoresis in which a multibarreled micropipette is used to record extracellular activity from a neuron while various agonists or antagonists are applied in the immediate vicinity. These studies showed that the characteristics of excitation by ACh are quite different from those produced by glutamate or other excitatory amino acids [78], [139]. One is a slow onset, requiring up to 30 s of ACh application

Long-lasting changes in single neuron activity following ACh application

Clear evidence that ACh can change the excitability of neurons for a long period after its application was provided in 1978 by Woody and his colleagues [154]. They paired the iontophoresis of ACh with intracellular depolarization of cortical neurons in awake cats. Approximately half of the cells showed a persistent (up to 1 h) change in membrane resistance. A similar proportion of neurons showed persistent membrane changes when cGMP iontophoresis was paired with depolarization, suggesting that

Identification of the pathways that can be facilitated by ACh

Numerous iontophoretic studies have shown that ACh can modulate neuronal responses along defined pathways, particularly in the sensory cortices where the thalamocortical pathway can be easily and selectively activated by the appropriate sensory input or by thalamic stimulation. These effects are quite similar in different sensory cortical areas and, when tested, appear to be mediated by muscarinic receptors. In cat visual cortex, ACh facilitates the response to visual stimulation, often with no

Neural pathways responsible for ACh release at cholinergic synapses

The cholinergic afferents to the cortex arise from the basal forebrain cholinergic neurons [134]. The anatomical evidence and the fact that electrical stimulation of the basal forebrain produces synaptic release of ACh in the neocortex provided the rationale for using basal forebrain stimulation to mimic the normal release of ACh. A number of studies have therefore studied cortical plasticity following basal forebrain stimulation. The main advantage of basal forebrain stimulation over

Lesion of the basal forebrain cholinergic system

The use of lesions to study the role of ACh in cortical plasticity has been hampered by the fact that cholinergic neurons are not clustered together in a localized nucleus that can be lesioned easily [134], [157]. Electrolytic lesions will destroy both non-cholinergic and cholinergic projection neurons as well as many intermingled neurons and axons of unknown function. Glutamate analogs such as ibotenic acid, quisqualate, NMDA and kainate, have been used to destroy cholinergic neurons but they

Conclusions

The data summarized in this review support the conclusion that cholinergic activation can induce plasticity in archi-, paleo-, and neocortex and may be essential in some situation. Several questions, however, remain to be answered: (1) how does ACh achieve this? (2) can all or only some connections be facilitated by ACh? and (3) how is this process regulated?

Acknowledgements

Supported by the Medical Research Council of Canada (MT-06673).

References (159)

  • E.C. Burgard et al.

    Muscarinic receptor activation facilitates the induction of long-term potentiation (LTP) in the rat dentate gyrus

    Neurosci. Lett.

    (1990)
  • F. Casamenti et al.

    Changes in cortical acetylcholine output induced by modulation of the nucleus basal

    Brain Res. Bull.

    (1986)
  • J.J. Chrobak et al.

    AF64A-induced working memory impairment: behavioral, neurochemical and histological correlates

    Brain Res.

    (1988)
  • J. Delacour et al.

    Evidence for a cholinergic mechanism of ‘learned’ changes in the responses of barrel field neurons of the awake and undrugged rat

    Neurosci.

    (1990)
  • J. Delacour et al.

    Learned changes in the responses of the rat barrel field neurons

    Neuroscience

    (1987)
  • L. Détári et al.

    Phasic relationship between the activity of basal forebrain neurons and cortical EEG in urethane-anesthetized rat

    Brain Res.

    (1997)
  • L. Détári et al.

    Activity of identified cortically projecting and other basal forebrain neurones during large slow waves and cortical activation in anaesthetized rats

    Brain Res.

    (1987)
  • J.P. Donoghue et al.

    Cholinergic modulation of sensory responses in rat primary somatic sensory cortex

    Brain Res.

    (1987)
  • J.D. Dudar

    The effect of septal nuclei stimulation on the release of acetylcholine from the rabbit hippocampus

    Brain Res.

    (1975)
  • M.G. Giovannini et al.

    Acetylcholine release from the frontal cortex during exploratory activity

    Brain Res.

    (1998)
  • M.G. Giovannini et al.

    Glutamatergic regulation of acetylcholine output in different brain regions: a microdialysis study in the rat

    Neurochem. Int.

    (1994)
  • J.V. Halliwell et al.

    Voltage-clamp analysis of muscarinic excitaiton in hippocampal neurons

    Brain Res.

    (1982)
  • I. Hanin

    The AF64A model of cholinergic hypofunction: an update

    Life Sci.

    (1996)
  • T. Hashimoto et al.

    Muscarinic M1 receptor mediated inhibition of GABA release from rat cerebral cortex

    Neurochem. Int.

    (1994)
  • A.M. Himmelheber et al.

    Effects of local cholinesterase inhibition on acetylcholine release assessed simultaneously in prefrontal and frontoparietal cortex

    Neuroscience

    (1998)
  • I. Hirotsu et al.

    Effect of anticholinergic drug on long-term potentiation in rat hippocampal slices

    Brain Res.

    (1989)
  • C.F. Höhmann et al.

    Neonatal lesions of the basal forebrain cholinergic neurons result in abnormal cortical development

    Dev. Brain Res.

    (1988)
  • M.E. Jiménez-Capdeville et al.

    Daily changes in the release of acetylcholine from rat primary somatosensory cortex

    Brain Res.

    (1993)
  • S. Kaneko et al.

    Cognitive enhancers and hippocampal long-term potentiation in vitro

    Behav. Brain Res.

    (1997)
  • A. Khateb et al.

    GABAergic input to cholinergic nucleus basalis neurons

    Neuroscience

    (1998)
  • K. Krnjevic et al.

    Electrophysiological and pharmacological characteristics of facilitation of hippocampal population spikes by stimulation of the medial septum

    Neuroscience

    (1982)
  • M. Kurosawa et al.

    Cutaneous mechanical sensory stimulation increases extracellular acetylcholine release in cerebral cortex in anesthetized rats

    Neurochem. Int.

    (1992)
  • M. Kurosawa et al.

    Stimulation of the nucleus basalis of Meynert increases acetylcholine release in the cerebral cortex in rats

    Neurosci. Lett.

    (1989)
  • Y. Lin et al.

    Muscarinic agonist-mediated induction of long-term potentiation in rat cerebral cortex

    Brain Res.

    (1991)
  • S.A. Lorens et al.

    Septal choline acetyltransferase immunoreactive neurons: dose-dependent effects of AF64A

    Brain Res. Bull.

    (1991)
  • T. Maeda et al.

    Roles of endogenous cholinergic neurons in the induction of long-term potentiation at hippocampal mossy fiber synapses

    Neurosci. Res.

    (1994)
  • D.C. Mash et al.

    Autoradiographic localization of M1 and M2 muscarine receptors in the rat brain

    Neuroscience

    (1986)
  • R. Metherate et al.

    Basal forebrain stimulation modifies auditory cortex responsiveness by an action at muscarinic receptors

    Brain Res.

    (1991)
  • R. Metherate et al.

    Acetylcholine permits long-term enhancement of neuronal responsiveness in cat primary somatosensory cortex

    Neuroscience

    (1987)
  • T. Akaishi et al.

    Responses of neurons in the nucleus basalis of Meynert to various afferent stimuli in rats

    Neuroreport

    (1990)
  • C. Aoki et al.

    Cholinergic terminals in the cat visual cortex: Ultrastructural basis for interaction with glutamate-immunoreactive neurons and other cells

    Vis. Neurosci.

    (1992)
  • M. Armstrong-James et al.

    An innocuous bias in whisker use in adult rats modifies receptive fields of barrel cortex neurons

    J. Neurosci.

    (1994)
  • J.H. Ashe et al.

    Cholinergic modulation of frequency receptive fields in auditory cortex: II. Frequency-specific effects of anticholinesterases provide evidence for a modulatory action of endogenous ACh

    Synapse

    (1989)
  • J.M. Auerbach et al.

    Muscarinic receptors mediating depression and long-term potentiation in rat hippocampus

    J. Physiol.

    (1996)
  • J.M. Auerbach et al.

    A novel cholinergic induction of long-term potentiation in rat hippocampus

    J. Neurophysiol.

    (1994)
  • J.S. Bakin et al.

    Induction of a physiological memory in the cerebral cortex by stimulation of the nucleus basalis

    Proc. Natl. Acad. Sci. USA

    (1996)
  • K.A. Baskerville et al.

    Topography of cholinergic afferents from the nucleus basalis of Meynert to representational areas of sensorimotor cortices in the rat

    J. Comp. Neurol.

    (1993)
  • M.F. Bear et al.

    Modulation of visual cortical plasticity by acetylcholine and noradrenaline

    Nature

    (1986)
  • L.S. Bernardo et al.

    Cholinergic excitation of mammalian hippocampal pyramidal cells

    Brain Res.

    (1982)
  • T.S. Bjordahl et al.

    Induction of long-term receptive field plasticity in the auditory cortex of the waking guinea pig by stimulation of the nucleus basalis

    Behav. Neurosci.

    (1998)
  • Cited by (0)

    View full text