Aged monkeys exhibit behavioral deficits indicative of widespread cerebral dysfunction

Bachevalier, Jocelyne; Landis, Linda S.; Walker, Lary C.; Brickson, Mimi; Mishkin, Mortimer; Price, Donald L.; Cork, Linda C.

doi:10.1016/0197-4580(91)90048-o

Cited by 250 publications

(166 citation statements)

References 48 publications

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“…Numerous efforts have been made to answer the question whether neuronal loss in the hippocampal formation and entorhinal cortex can, at least in part, accounts for age-related decline in cognitive processes such as learning and memory [4,5,21,37,38]. In earlier studies, most of the data were reported as neuron density per unit volume or area, but this literature on neuronal numbers in the hippocampal formation, for example, shows much controversy.…”

Section: Introductionmentioning

confidence: 93%

Preservation of hippocampal neuron numbers in aged rhesus monkeys

Keuker

Luiten

Fuchs

2003

Neurobiology of Aging

122

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Preservation of hippocampal neuron numbers in aged rhesus monkeys Keuker, J.I.H.; Luiten, P.G.M.; Fuchs, E. Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. AbstractTo investigate whether or not aging of nonhuman primates is accompanied by a region-specific neuron loss in the hippocampal formation, we used the optical fractionator technique to obtain stereological estimates of unilateral neuron numbers of the hippocampi of eight young (0-4 years) and five aged (18-31 years) male rhesus monkeys (Macaca mulatta). Our results show a preservation of neurons (mean × 10 3 ± S.D. × 10 3 ) in the subiculum (young = 588 ± 124, aged = 612 ± 207), CA1 (young = 1051 ± 249, aged = 1318 ± 311), CA2 (young = 100 ± 18, aged = 113 ± 12), CA3 (young = 478 ± 125, aged = 509 ± 139), hilus (young = 337 ± 115, aged = 394 ± 90), and dentate gyrus (young = 5550 ± 1725, aged = 7799 ± 2087) of the hippocampal formation. These results confirm a previous stereological study in rhesus monkeys, but are in conflict with data for humans, showing age-dependent region-specific alterations in the hippocampal formation.

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Section: Introductionmentioning

confidence: 93%

Preservation of hippocampal neuron numbers in aged rhesus monkeys

Keuker

Luiten

Fuchs

2003

Neurobiology of Aging

122

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“…Age-related cognitive decline begins as early as the late teens in rhesus monkeys, although as in humans, some aged monkeys are resistant to the decline and exhibit cognitive abilities similar to those of young adults (Presty et al 1987;Bachevalier et al 1991;Rapp and Amaral 1991;Peters et al 1996). Additionally, not all functional abilities are affected equally within an individual aged monkey (Voytko 1999).…”

Section: Nonhuman Primate As a Model Of Agingmentioning

confidence: 99%

“…1). Aged monkeys require more trials to acquire this task, and they perform significantly and disproportionately worse at longer delay intervals compared to young monkeys (Bartus et al 1978;Rapp and Amaral 1989;Bachevalier et al 1991;Voytko and Tinkler 2004).…”

Section: Delayed Responsementioning

confidence: 99%

Neuronal and morphological bases of cognitive decline in aged rhesus monkeys

Hara

Rapp

Morrison

2011

AGE

120

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Rhesus monkeys provide a valuable model for studying the basis of cognitive aging because they are vulnerable to age-related decline in executive function and memory in a manner similar to humans. Some of the behavioral tasks sensitive to the effects of aging are the delayed response working memory test, recognition memory tests including the delayed nonmatching-to-sample and the delayed recognition span task, and tests of executive function including reversal learning and conceptual set-shifting task. Much effort has been directed toward discovering the neurobiological parameters that are coupled to individual differences in age-related cognitive decline. Area 46 of the dorsolateral prefrontal cortex (dlPFC) has been extensively studied for its critical role in executive function while the hippocampus and related cortical regions have been a major target of research for memory function. Some of the key age-related changes in area 46 include decreases in volume, microcolumn strength, synapse density, and α1-and α2-adrenergic receptor binding densities. All of these measures significantly correlate with cognitive scores. Interestingly, the critical synaptic subtypes associated with cognitive function appear to be different between the dlPFC and the hippocampus. For example, the dendritic spine subtype most critical to task acquisition and vulnerable to aging in area 46 is the thin spine, whereas in the dentate gyrus, the density of AGE (2012) large mushroom spines with perforated synapses correlates with memory performance. This review summarizes age-related changes in anatomical, neuronal, and synaptic parameters within brain areas implicated in cognition and whether these changes are associated with cognitive decline.

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“…Across all species studies have found that the memory deficit associated with aging is characterized by large variability in cognitive capacities so that some aged subjects perform as well young subjects, whereas others show severe impairment (Markowska et al, 1989;Bachevalier et al, 1991;Rapp and Amaral, 1992;Gallagher et al, 1993). Many experiments have identified anatomical, molecular, and physiological markers of memory impairment in the hippocampal region of aged animals and humans (Barnes, 1979(Barnes, , 1988DeToledo-Morrell et al, 1988;Gage et al, 1988;Rapp and Amaral, 1992; Gallagher et al, 1994;Rapp and Heindel, 1994;Grady et al, 1995;Rapp and Gallagher, 1996), but few studies to date have characterized age-associated changes in the nature of information encoded by neurons in the brain.…”

Section: Abstract: Spatial Learning; Spatial Memory; Place Field; Elmentioning

confidence: 99%

Brain Aging: Changes in the Nature of Information Coding by the Hippocampus

et al. 1997

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Advanced age in rats is associated with a decline in spatial memory capacities dependent on hippocampal processing. As yet, however, little is known about the nature of age-related alterations in the information encoded by the hippocampus. Young rats and aged rats identified as intact or impaired in spatial learning capacity were trained on a radial arm maze task, and then multiple parameters of the environmental cues were manipulated to characterize the changes in firing patterns of hippocampal neurons corresponding to the presence of particular cues or the spatial relationships among them. The scope of information encoded by the hippocampus was reduced in memory-impaired aged subjects, even though the number of neurons responsive to salient environmental cues was not different from that in young rats. Furthermore, after repeated manipulations of the cues, memory-intact aged rats, like young rats, altered their spatial representations, whereas memory-impaired aged rats showed reduced plasticity of their representation throughout testing. Thus changes in hippocampal memory representation associated with aging and memory loss can be characterized as a rigid encoding of only part of the available information. Key words: spatial learning; spatial memory; place field; electrophysiology; encoding; representation; rat; ageDiminished memory capacity is a well known concomitant of aging in humans (Craik, 1990;Rapp and Heindel, 1994) and animals (Barnes, , 1988DeToledo-Morrell et al., 1988;Gage et al., 1988;Rapp and Amaral, 1992;Rapp and Heindel, 1994;Gallagher et al., 1995). Across all species studies have found that the memory deficit associated with aging is characterized by large variability in cognitive capacities so that some aged subjects perform as well young subjects, whereas others show severe impairment (Markowska et al., 1989;Bachevalier et al., 1991;Rapp and Amaral, 1992;Gallagher et al., 1993). Many experiments have identified anatomical, molecular, and physiological markers of memory impairment in the hippocampal region of aged animals and humans (Barnes, 1979(Barnes, , 1988DeToledo-Morrell et al., 1988;Gage et al., 1988;Rapp and Amaral, 1992; Gallagher et al., 1994;Rapp and Heindel, 1994;Grady et al., 1995;Rapp and Gallagher, 1996), but few studies to date have characterized age-associated changes in the nature of information encoded by neurons in the brain.In rats aging results in an impairment in spatial learning and memory. Spatial learning in rats is strongly dependent on hippocampal function (Morris et al., 1982), and the firing patterns of hippocampal pyramidal cells correlate with the spatial location of an animal in the testing environment during exploratory behavior (O' Keefe and Nadel, 1978). The firing pattern of such hippocampal "place cells" is controlled by spatial and other relationships among multiple environmental cues and ongoing behavior and may reflect higher-order memory processing (O'Keefe and Nadel, 1978;Muller and Kubie, 1987;Eichenbaum, 1996).The activity of place cells in rats ex...

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Aged monkeys exhibit behavioral deficits indicative of widespread cerebral dysfunction

Cited by 250 publications

References 48 publications

Preservation of hippocampal neuron numbers in aged rhesus monkeys

Preservation of hippocampal neuron numbers in aged rhesus monkeys

Neuronal and morphological bases of cognitive decline in aged rhesus monkeys

Brain Aging: Changes in the Nature of Information Coding by the Hippocampus

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