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