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Neuronal and morphological bases of cognitive decline in aged rhesus monkeys

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Abstract

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 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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Acknowledgments

Original research and manuscript preparation was supported by National Institute on Aging grants R37 AG06647, R01 AG010606, P01 AG16765 to J.H.M. and in part by the Intramural Research Program of the National Institute on Aging. This manuscript was prepared while Y.H. was an Ellison Medical Foundation/AFAR Postdoctoral Fellow. We thank Erik Bloss for critical discussion and helpful comments on the manuscript.

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Authors and Affiliations

  1. Fishberg Department of Neuroscience and Kastor Neurobiology of Aging Laboratories, Mount Sinai School of Medicine, New York, NY, 10029, USA

    Yuko Hara & John H. Morrison

  2. Friedman Brain Institute, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1065, New York, NY, 10029, USA

    Yuko Hara & John H. Morrison

  3. Department of Geriatrics and Palliative Medicine, Mount Sinai School of Medicine, New York, NY, 10029, USA

    John H. Morrison

  4. Computational Neurobiology and Imaging Center, Mount Sinai School of Medicine, New York, NY, 10029, USA

    John H. Morrison

  5. Laboratory of Experimental Gerontology, National Institute on Aging, Baltimore, MD, 21224, USA

    Peter R. Rapp

  6. Department of Neuroscience, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1065, New York, NY, 10029, USA

    John H. Morrison

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  1. Yuko Hara
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  2. Peter R. Rapp
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Correspondence to John H. Morrison.

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Hara, Y., Rapp, P.R. & Morrison, J.H. Neuronal and morphological bases of cognitive decline in aged rhesus monkeys. AGE 34, 1051–1073 (2012). https://doi.org/10.1007/s11357-011-9278-5

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