Reduction in hippocampal cholinergic innervation is unrelated to recognition memory impairment in aged rhesus monkeys

Michael E. Calhoun, Ying Mao, Jeffrey A Roberts, Peter R. Rapp

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Alterations in the basal forebrain cholinergic system have been widely studied in brain aging and Alzheimer's disease, but the magnitude of decline and relationship to cognitive impairment are still a matter of debate. The rhesus monkey (Macaca mulatta) provides a compelling model to study age-related memory decline, as the pattern of impairment closely parallels that observed in humans. Here, we used antibodies against the vesicular acetylcholine transporter and a new stereological technique to estimate total cholinergic fiber length in hippocampal subregions of behaviorally characterized young and aged rhesus monkeys. The analysis revealed an age-related decline in the length of cholinergic fibers of 22%, which was similar across the hippocampal subregions studied (dentate gyrus granule cell and molecular layers, CA2/3-hilus, and CA1), and across the rostral-caudal extent of the hippocampus. This effect, however, was unrelated to performance on the delayed nonmatching-to-sample task, a test of recognition memory sensitive to hippocampal system dysfunction and cognitive aging in monkeys. These findings indicate that a decline in cholinergic input fails to account for the influence of normal aging on memory supported by the primate hippocampal region.

Original languageEnglish (US)
Pages (from-to)238-246
Number of pages9
JournalJournal of Comparative Neurology
Volume475
Issue number2
DOIs
StatePublished - Jul 19 2004

Fingerprint

Macaca mulatta
Cholinergic Fibers
Cholinergic Agents
Vesicular Acetylcholine Transport Proteins
Dentate Gyrus
Brain Diseases
Primates
Haplorhini
Hippocampus
Alzheimer Disease
Antibodies
Recognition (Psychology)

Keywords

  • Acetylcholine
  • Aging
  • Cognition
  • Hippocampus
  • Nonhuman primate
  • Stereology
  • Terms

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Reduction in hippocampal cholinergic innervation is unrelated to recognition memory impairment in aged rhesus monkeys. / Calhoun, Michael E.; Mao, Ying; Roberts, Jeffrey A; Rapp, Peter R.

In: Journal of Comparative Neurology, Vol. 475, No. 2, 19.07.2004, p. 238-246.

Research output: Contribution to journalArticle

@article{2ea30baf3f204e91958b229b47dcb8e7,
title = "Reduction in hippocampal cholinergic innervation is unrelated to recognition memory impairment in aged rhesus monkeys",
abstract = "Alterations in the basal forebrain cholinergic system have been widely studied in brain aging and Alzheimer's disease, but the magnitude of decline and relationship to cognitive impairment are still a matter of debate. The rhesus monkey (Macaca mulatta) provides a compelling model to study age-related memory decline, as the pattern of impairment closely parallels that observed in humans. Here, we used antibodies against the vesicular acetylcholine transporter and a new stereological technique to estimate total cholinergic fiber length in hippocampal subregions of behaviorally characterized young and aged rhesus monkeys. The analysis revealed an age-related decline in the length of cholinergic fibers of 22{\%}, which was similar across the hippocampal subregions studied (dentate gyrus granule cell and molecular layers, CA2/3-hilus, and CA1), and across the rostral-caudal extent of the hippocampus. This effect, however, was unrelated to performance on the delayed nonmatching-to-sample task, a test of recognition memory sensitive to hippocampal system dysfunction and cognitive aging in monkeys. These findings indicate that a decline in cholinergic input fails to account for the influence of normal aging on memory supported by the primate hippocampal region.",
keywords = "Acetylcholine, Aging, Cognition, Hippocampus, Nonhuman primate, Stereology, Terms",
author = "Calhoun, {Michael E.} and Ying Mao and Roberts, {Jeffrey A} and Rapp, {Peter R.}",
year = "2004",
month = "7",
day = "19",
doi = "10.1002/cne.20181",
language = "English (US)",
volume = "475",
pages = "238--246",
journal = "Journal of Comparative Neurology",
issn = "0021-9967",
publisher = "Wiley-Liss Inc.",
number = "2",

}

TY - JOUR

T1 - Reduction in hippocampal cholinergic innervation is unrelated to recognition memory impairment in aged rhesus monkeys

AU - Calhoun, Michael E.

AU - Mao, Ying

AU - Roberts, Jeffrey A

AU - Rapp, Peter R.

PY - 2004/7/19

Y1 - 2004/7/19

N2 - Alterations in the basal forebrain cholinergic system have been widely studied in brain aging and Alzheimer's disease, but the magnitude of decline and relationship to cognitive impairment are still a matter of debate. The rhesus monkey (Macaca mulatta) provides a compelling model to study age-related memory decline, as the pattern of impairment closely parallels that observed in humans. Here, we used antibodies against the vesicular acetylcholine transporter and a new stereological technique to estimate total cholinergic fiber length in hippocampal subregions of behaviorally characterized young and aged rhesus monkeys. The analysis revealed an age-related decline in the length of cholinergic fibers of 22%, which was similar across the hippocampal subregions studied (dentate gyrus granule cell and molecular layers, CA2/3-hilus, and CA1), and across the rostral-caudal extent of the hippocampus. This effect, however, was unrelated to performance on the delayed nonmatching-to-sample task, a test of recognition memory sensitive to hippocampal system dysfunction and cognitive aging in monkeys. These findings indicate that a decline in cholinergic input fails to account for the influence of normal aging on memory supported by the primate hippocampal region.

AB - Alterations in the basal forebrain cholinergic system have been widely studied in brain aging and Alzheimer's disease, but the magnitude of decline and relationship to cognitive impairment are still a matter of debate. The rhesus monkey (Macaca mulatta) provides a compelling model to study age-related memory decline, as the pattern of impairment closely parallels that observed in humans. Here, we used antibodies against the vesicular acetylcholine transporter and a new stereological technique to estimate total cholinergic fiber length in hippocampal subregions of behaviorally characterized young and aged rhesus monkeys. The analysis revealed an age-related decline in the length of cholinergic fibers of 22%, which was similar across the hippocampal subregions studied (dentate gyrus granule cell and molecular layers, CA2/3-hilus, and CA1), and across the rostral-caudal extent of the hippocampus. This effect, however, was unrelated to performance on the delayed nonmatching-to-sample task, a test of recognition memory sensitive to hippocampal system dysfunction and cognitive aging in monkeys. These findings indicate that a decline in cholinergic input fails to account for the influence of normal aging on memory supported by the primate hippocampal region.

KW - Acetylcholine

KW - Aging

KW - Cognition

KW - Hippocampus

KW - Nonhuman primate

KW - Stereology

KW - Terms

UR - http://www.scopus.com/inward/record.url?scp=3042769201&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=3042769201&partnerID=8YFLogxK

U2 - 10.1002/cne.20181

DO - 10.1002/cne.20181

M3 - Article

C2 - 15211464

AN - SCOPUS:3042769201

VL - 475

SP - 238

EP - 246

JO - Journal of Comparative Neurology

JF - Journal of Comparative Neurology

SN - 0021-9967

IS - 2

ER -