Cited by 200Memory and Neural MechanismsNeuroscience and Neuropharmacology ResearchCholinesterase and Neurodegenerative Diseases

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Excitotoxic lesions of basal forebrain cholinergic neurons: Effects on learning, memory and attention

Muir, Janice L., Page, Keith J., Sirinathsinghji, D.J.S., Robbins, Trevor W., Everitt, Barry J.·1993·Behavioural Brain Research

DOI 10.1016/0166-4328(93)90128-d

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Abstract

A substantial body of literature has suggested that the memory and learning deficits associated with Alzheimer's disease are attributable to degeneration of the cholinergic magnocellular neurons of the nucleus basalis of Meynert (nbM). Subsequently, lesion-induced damage to the cholinergic projections from the nbM to the neocortex has been utilized extensively as an animal model of dementia. Ibotenic acid lesions of the basal forebrain have been found, for example, to produce deficits in a wide variety of tasks involving learning and memory. However, recently, with the availability of more potent cholinergic excitotoxins such as AMPA, it has become apparent that nbM lesions do not provide a simple animal model of the cognitive deficits in ageing and Alzheimer's disease. Further analysis suggests that many of the learning and memory impairments traditionally attributed to the cholinergic corticopetal system are due not to destruction of cholinergic neurons in the nbM, but instead result from the disruption of cortico-striatal outputs passing through the dorsal and ventral globus pallidus. Furthermore, experiments utilizing quisqualic acid and AMPA have revealed that the most convincing deficit observed as a result of such lesions is in visual attention. This role for the basal forebrain-cortical cholinergic system in attentional function is further supported by results obtained from complementary pharmacological studies. This does not exclude a role for acetylcholine in learning and memory processes. Rather, such cognitive processes appear to depend not upon the integrity of the nbM itself, but upon more rostral elements of the cholinergic basal forebrain system.

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Untitled work
(1998) · doi:10.1002/(sici)1097-4695(199812)37:4

Authors: Muir, J. L., Page, K. J., Sirinathsinghji, D. J. S., Robbins, T. W., & Everitt, B. J.
Affiliations: University of Cambridge (GB)
Corresponding author: Everitt, Barry J.
ORCID: Page, Keith J.
Robbins, Trevor W.
Everitt, Barry J.
Venue: Behavioural Brain Research
Publisher: Elsevier BV
Published: 1993-11
Volume: 57
Issue: 2
Pages: 123-131
ISSN: 0166-4328 (ISSN-L)
DOI: 10.1016/0166-4328(93)90128-d
OpenAlex: W2052625961
Cited by: 199
References: 30
Citations by year: 2026: 2 · 2025: 2 · 2024: 3 · 2023: 1 · 2021: 4 · 2020: 4 · 2019: 4 · 2018: 6 · 2017: 3 · 2016: 9 · 2015: 7 · 2014: 9 · 2013: 9 · 2012: 1
FWCI: 1.57
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Behavioural Brain Research (publishedVersion)
PubMed (publishedVersion)
Funders: Wellcome Trust
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
Keywords: excitotoxic lesions, cholinergic neurons, basal forebrain, nucleus basalis of Meynert, Alzheimer's disease, learning and memory impairment, visual attention, globus pallidus, corticostriatal pathway, ibotenic acid, quisqualic acid, AMPA, animal models of dementia, acetylcholine
MeSH terms: Acetylcholine, Alzheimer Disease, Animals, Attention, Brain Mapping, Cerebral Cortex, Cholinergic Fibers, Disease Models, Animal, Humans, Learning, Memory, Substantia Innominata, Prosencephalon, Receptors, AMPA, alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid

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Excitotoxic lesions of basal forebrain cholinergic neurons: Effects on learning, memory and attention

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