Role of cholinergic system on the construction of memories: Taste memory encoding

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Abstract

There is a large body of evidence suggesting that cholinergic activity is involved in memory processes. It seems that cholinergic activity is essential to learn several tasks and recent works suggest that acetylcholine plays an important role during the early stages of memory formation. In this review, we will discuss the results related to taste memory formation, focusing particularly on the conditioned taste aversion paradigm. We will first give evidence that nucleus basalis magnocellularis is involved in taste memory formation, due to its cholinergic projections. We then show that the cholinergic activity of the insular (gustatory) cortex is related to the taste novelty, and that the cholinergic signals initiated by novelty are crucial for taste memory formation. Then we present recent data indicating that cortical activation of muscarinic receptors is necessary for taste trace encoding, and also for its consolidation under certain circumstances. Finally, interactions between the cholinergic and other neuromodulatory systems inducing intracellular mechanisms related to plastic changes will be proposed as important processes underlying gustatory memory trace storage.

Introduction

A substantial body of literature has suggested that in humans memory deficits associated with Alzheimer’s disease and normal aging can be attributed to degeneration of cholinergic basal forebrain neurons (for review: Muir, 1997). Thus, numerous anatomical and behavioral studies were developed to investigate in animals the relationship between the neurons located in this basal forebrain complex and the maintenance of normal cognitive functions. Furthermore, in recent years accumulated evidence demonstrates that the cholinergic receptors set off a series of intracellular events related to the plasticity of the central nervous system related with memory encoding.

Behavioral studies on animal models demonstrate that lesion-induced damage to the nucleus basalis magnocellularis (NBM), and their cholinergic projections from to the neocortex induce deficits related to cognitive impairments, especially on attentional processes (for review: Sarter & Bruno, 1997), as well as on learning and memory processes (for review: Dunnett, 1993; Dunnett, Everitt, & Robbins, 1991; Everitt & Robbins, 1997; Wenk, 1997; Woolf, 1998). The assumption that cortical cholinergic projections were involved in learning and memory was also reinforced by studies related to cortical acetylcholine (ACh) activity. In this regard, it has been demonstrated, for example, that ACh modifies cellular responses in vivo, and modulates receptive plastic changes in the auditory cortex (Metherate & Ashe, 1993; Weinberger & Bakin, 1998) and somatosensory cortex (Dykes, Metherate, & Tremblay, 1990). Cortical ACh was thus hypothesized to modulate the general efficacy of the cortical processing of sensory or associational information. Specifically, cortical cholinergic inputs could mediate the subjects’ abilities to detect and select stimuli and associations for extended processing and to allocate the appropriate processing resources to these functions. Some authors proposed that the cholinergic system participates in higher cognitive functions through neural network modeling (for review: Myers et al., 1996).

The purpose of this paper is to provide recent evidence about the stages in which the cholinergic activity is involved in memory formation. We will give evidence that the cholinergic system plays an important role during the early stages of taste memory formation, by modulating the signaling of the taste novelty, and then participating in several intracellular mechanisms related to plastic events that could be essential for taste memory encoding.

Section snippets

Conditioned taste aversion and forebrain structures

A reliable and robust paradigm to study the different processes during taste memory formation is the conditioned taste aversion (CTA). CTA is an example of adaptive learning in which an animal acquires aversion to a novel taste, the conditioned stimulus (CS), when it is followed by digestive malaise, generally induced by lithium chloride (LiCl), the unconditioned stimulus (US). The anatomical substrates responsible for CTA learning have been well established (see Bermudez-Rattoni & Yamamoto,

Nucleus basalis magnocellularis

The cholinergic basal forebrain complex is a group of relatively large neurons located in the ventral region of the mammalian brain. It includes the medial septal area, the vertical and horizontal limbs of the diagonal band of Broca, and the nucleus basalis of Meynert in humans and primates, also called the NBM in the other mammals. The basal forebrain complex provides widespread cholinergic, and also GABAergic, innervations throughout the brain: the septal area and the vertical limb of the

Cortical muscarinic receptors

The preceding paragraphs stressed the importance of the IC, and particularly the cholinergic afferents from NBM to this cortical area in taste aversion memory formation. In the following section we will present evidence of the importance of cortical cholinergic receptors in taste memory formation and try to understand to what extent they participate in the mnemonic processes.

In recent years, the study of the role of different nicotinic and muscarinic receptors subtypes in learning and memory

Interactions with other neurotransmitter systems

One of the most interesting interactions between different neurotransmitters is probably the related activity between ACh and glutamate, thereby initiating cellular plastic events via NMDA receptors that activate a number of protein kinases in the post-synaptic cell related to long-term memory formation (Woolf, 1996). The interaction between muscarinic ACh receptors with NMDA glutamate receptors is notably critical to memory (Woolf, 1998). There are a number of studies stressing the importance

Plasticity changes

One of the interesting features of the activation of muscarinic receptors is the initiation of a series of extracellular signal-regulated kinases 1/2 (ERK 1/2) pathway activity, which has been linked to several forms of synaptic plasticity (Orban, Chapman, & Brambilla, 1999) including LTP (English & Sweatt, 1997). As noted, LTP in the cortex and hippocampus is modulated by muscarinic receptors (Jones et al., 1999) and low doses of carbachol can induce prolonged activation of ERK 1/2 in primary

Conclusion: From novelty to memory encoding

We have been developing a working model that may partially explain the action of the cholinergic system during the different stages of taste memory formation and its interaction with the glutamate NMDA activation (Fig. 4). Thus, consumption of a novel taste induces activation of the NBM and especially its cholinergic projections to the IC and amygdala (Gutierrez et al., 1999a; Gutierrez et al., 1999b; Miranda & Bermudez-Rattoni, 1999; Otawa, Takagi, & Ogawa, 1995). In IC, a significant

Acknowledgements

This work was supported by CONACYT-Mexico Grants MRI 35806-N and 31842-N DGAPA-IN215001 (F.B.R.) and INRA MRI/AR2003 (G.F.). We give thanks to Shaun Harris, for the English revision of the final text.

References (85)

  • M.G. Giovannini et al.

    Effects of novelty and habituation on acetylcholine, GABA, and glutamate release from the frontal cortex and hippocampus of freely moving rats

    Neuroscience

    (2001)
  • C. Gonzalez et al.

    Differential participation of the NBM in the acquisition and retrevial of conditioned taste aversion and Morris water maze

    Behavioural Brain Research

    (2000)
  • H. Gutierrez et al.

    Differential effects of 192IgG-saporin and NMDA-induced lesions into the basal forebrain on cholinergic activity and taste aversion memory formation

    Brain Research

    (1999)
  • H. Gutierrez et al.

    Blockade of N-methyl-d-aspartate receptors in the insular cortex disrupts taste aversion and spatial memory formation

    Neuroscience

    (1999)
  • R. Gutierrez et al.

    Cholinergic dependence of taste memory formation: Evidence of two distinct processes

    Neurobiology of Learning and Memory

    (2003)
  • S. Heckers et al.

    Two types of cholinergic projections to the rat amygdala

    Neuroscience

    (1994)
  • L.A. Izquierdo et al.

    Short- and long-term memory are differentially affected by metabolic inhibitors given into hippocampus and entorhinal cortex

    Neurobiology of Learning and Memory

    (2000)
  • R.P. Kesner et al.

    Place and taste aversion learning: Role of basal forebrain, parietal cortex, and amygdala

    Brain Research Bulletin

    (1992)
  • P.E. Mallet et al.

    Nucleus basalis lesions: Implication of basoamygdaloid cholinergic pathways in memory

    Brain Research Bulletin

    (1995)
  • J.L. McGaugh

    Memory consolidation and the amygdala: A systems perspective

    Trends in Neuroscience

    (2002)
  • L. Minichiello et al.

    Essential role for TrkB receptors in hippocampus-mediated learning

    Neuron

    (1999)
  • M.I. Miranda et al.

    Cortical cholinergic activity is related to the novelty of the stimulus

    Brain Research

    (2000)
  • I. Moron et al.

    Differential effects of bicuculline and muscimol microinjections into the nucleus basalis magnocellularis in taste and place aversive memory formation

    Behavioural Brain Research

    (2002)
  • J.L. Muir

    Acetylcholine, aging, and Alzheimer’s disease

    Pharmacology, Biochemistry, and Behaviour

    (1997)
  • C.E. Myers et al.

    A computational model of cholinergic disruption of septohippocampal activity in classical eyeblink conditioning

    Neurobiology of Learning and Memory

    (1996)
  • C. Naor et al.

    Transient impairment of cholinergic function in the rat insular cortex disrupts the encoding of taste in conditioned taste aversion

    Behavioural Brain Research

    (1996)
  • M. Ohno et al.

    Noradrenergic DSP-4 lesions aggravate impairment of working memory produced by hippocampal muscarinic blockade in rats

    Pharmacology, Biochemistry, and Behaviour

    (1997)
  • P.C. Orban et al.

    Is the Ras-MAPK signalling pathway necessary for long-term memory formation?

    Trends in Neuroscience

    (1999)
  • M. Orsetti et al.

    Enhanced acetylcholine release in the hippocampus and cortex during acquisition of an operant behavior

    Brain Research

    (1996)
  • M.G. Packard et al.

    Post-training injection of the acetylcholine M2 receptor antagonist AF-DX 116 improves memory

    Brain Research

    (1990)
  • A.E. Power et al.

    Phthalic acid amygdalopetal lesion of the nucleus basalis magnocellularis induces reversible memory deficits in rats

    Neurobiology of Learning and Memory

    (2002)
  • L. Ramirez-Lugo et al.

    The role of cortical cholinergic pre- and post-synaptic receptors in taste memory formation

    Neurobiology of Learning and Memory

    (2003)
  • G. Roldan et al.

    Tetrodotoxin blockade of amygdala overlapping with poisoning impairs acquisition of conditioned taste aversion in rats

    Behavioural Brain Research

    (1994)
  • K. Rosenblum et al.

    Taste memory: The role of protein synthesis in gustatory cortex

    Behavioural and Neural Biology

    (1993)
  • M. Sarter et al.

    Cognitive functions of cortical acetylcholine: Toward a unifying hypothesis

    Brain Research. Brain Research Reviews

    (1997)
  • D.G.J. Spencer et al.

    Direct autoradiographic determination of M1 and M2 muscarinic acetylcholine receptor distribution in the rat brain: Relation to cholinergic nuclei and projections

    Brain Research

    (1986)
  • C.M. Thiel et al.

    Hippocampal acetylcholine and habituation learning

    Neuroscience

    (1998)
  • C.H. Vanderwolf

    Near-total loss of ‘learning’ and ‘memory’ as a result of combined cholinergic and serotonergic blockade in the rat

    Behavioural Brain Research

    (1987)
  • G.L. Wenk

    The nucleus basalis magnocellularis cholinergic system: One hundred years of progress

    Neurobiology of Learning and Memory

    (1997)
  • N.J. Woolf

    The critical role of cholinergic basal forebrain neurons in morphological change and memory encoding: A hypothesis

    Neurobiology of Learning and Memory

    (1996)
  • N.J. Woolf

    A structural basis for memory storage in mammals

    Progress in Neurobiology

    (1998)
  • Y. Yasoshima et al.

    Different disruptive effects on the acquisition and expression of conditioned taste aversion by blockades of amygdalar ionotropic and metabotropic glutamatergic receptor subtypes in rats

    Brain Research

    (2000)
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