Lesions of the basal forebrain cholinergic system in mice disrupt idiothetic navigation

Hamlin, Adam S., Windels, Francois, Boskovic, Zoran, Sah, Pankaj and Coulson, Elizabeth J. (2013) Lesions of the basal forebrain cholinergic system in mice disrupt idiothetic navigation. PLoS ONE, 8 1: e53472.1-e53472.9. doi:10.1371/journal.pone.0053472

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Author Hamlin, Adam S.
Windels, Francois
Boskovic, Zoran
Sah, Pankaj
Coulson, Elizabeth J.
Title Lesions of the basal forebrain cholinergic system in mice disrupt idiothetic navigation
Journal name PLoS ONE   Check publisher's open access policy
ISSN 1932-6203
Publication date 2013-01-08
Sub-type Article (original research)
DOI 10.1371/journal.pone.0053472
Open Access Status DOI
Volume 8
Issue 1
Start page e53472.1
End page e53472.9
Total pages 9
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2014
Language eng
Abstract Loss of integrity of the basal forebrain cholinergic neurons is a consistent feature of Alzheimer's disease, and measurement of basal forebrain degeneration by magnetic resonance imaging is emerging as a sensitive diagnostic marker for prodromal disease. It is also known that Alzheimer's disease patients perform poorly on both real space and computerized cued (allothetic) or uncued (idiothetic) recall navigation tasks. Although the hippocampus is required for allothetic navigation, lesions of this region only mildly affect idiothetic navigation. Here we tested the hypothesis that the cholinergic medial septo-hippocampal circuit is important for idiothetic navigation. Basal forebrain cholinergic neurons were selectively lesioned in mice using the toxin saporin conjugated to a basal forebrain cholinergic neuronal marker, the p75 neurotrophin receptor. Control animals were able to learn and remember spatial information when tested on a modified version of the passive place avoidance test where all extramaze cues were removed, and animals had to rely on idiothetic signals. However, the exploratory behaviour of mice with cholinergic basal forebrain lesions was highly disorganized during this test. By contrast, the lesioned animals performed no differently from controls in tasks involving contextual fear conditioning and spatial working memory (Y maze), and displayed no deficits in potentially confounding behaviours such as motor performance, anxiety, or disturbed sleep/wake cycles. These data suggest that the basal forebrain cholinergic system plays a specific role in idiothetic navigation, a modality that is impaired early in Alzheimer's disease.
Keyword Alzheimer’s disease
Basal forebrain degeneration
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2014 Collection
 
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Citation counts: TR Web of Science Citation Count  Cited 8 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 9 times in Scopus Article | Citations
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Created: Tue, 12 Feb 2013, 16:35:53 EST by Debra McMurtrie on behalf of Queensland Brain Institute