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

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 d...

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Autores principales:	Adam S Hamlin, Francois Windels, Zoran Boskovic, Pankaj Sah, Elizabeth J Coulson
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/53af3b3fb4724ddcbdfeca066dac0586
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spelling	oai:doaj.org-article:53af3b3fb4724ddcbdfeca066dac05862021-11-18T08:02:19ZLesions of the basal forebrain cholinergic system in mice disrupt idiothetic navigation.1932-620310.1371/journal.pone.0053472https://doaj.org/article/53af3b3fb4724ddcbdfeca066dac05862013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23320088/?tool=EBIhttps://doaj.org/toc/1932-6203Loss 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.Adam S HamlinFrancois WindelsZoran BoskovicPankaj SahElizabeth J CoulsonPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e53472 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Adam S Hamlin Francois Windels Zoran Boskovic Pankaj Sah Elizabeth J Coulson Lesions of the basal forebrain cholinergic system in mice disrupt idiothetic navigation.
description	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.
format	article
author	Adam S Hamlin Francois Windels Zoran Boskovic Pankaj Sah Elizabeth J Coulson
author_facet	Adam S Hamlin Francois Windels Zoran Boskovic Pankaj Sah Elizabeth J Coulson
author_sort	Adam S Hamlin
title	Lesions of the basal forebrain cholinergic system in mice disrupt idiothetic navigation.
title_short	Lesions of the basal forebrain cholinergic system in mice disrupt idiothetic navigation.
title_full	Lesions of the basal forebrain cholinergic system in mice disrupt idiothetic navigation.
title_fullStr	Lesions of the basal forebrain cholinergic system in mice disrupt idiothetic navigation.
title_full_unstemmed	Lesions of the basal forebrain cholinergic system in mice disrupt idiothetic navigation.
title_sort	lesions of the basal forebrain cholinergic system in mice disrupt idiothetic navigation.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/53af3b3fb4724ddcbdfeca066dac0586
work_keys_str_mv	AT adamshamlin lesionsofthebasalforebraincholinergicsysteminmicedisruptidiotheticnavigation AT francoiswindels lesionsofthebasalforebraincholinergicsysteminmicedisruptidiotheticnavigation AT zoranboskovic lesionsofthebasalforebraincholinergicsysteminmicedisruptidiotheticnavigation AT pankajsah lesionsofthebasalforebraincholinergicsysteminmicedisruptidiotheticnavigation AT elizabethjcoulson lesionsofthebasalforebraincholinergicsysteminmicedisruptidiotheticnavigation
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Lesions of the basal forebrain cholinergic system in mice disrupt idiothetic navigation.

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