Experiments proposed in this application bring into convergence current progress from the broader field of learning and memory research with recent findings in aged monkeys, toward addressing a new generation of questions concerning the neurobiology of normal cognitive aging in primates. The overall aims of the research program are to define the effects of normal aging on the information processing capacities that enable episodic memory, and to test the proposal that age-related decline results from large-scale restructuring of the neural networks critical for memory, regulated in part by ovarian senescence. Fourteen young adult (~5-10 years) and 18 aged (~22-28 years) female rhesus monkeys will be tested across an extensive neuropsychological battery consisting of both conventional, well-established procedures, including repeated assessment on the classic delayed response test, and a number of recently validated tasks aimed at assessing key operating characteristics of memory. Including standard tests of learning and memory is important to provide continuity with our earlier behavioral studies, and importantly, to establish a baseline for gauging the relative sensitivity and selectivity of newer tests to age-related impairment. These latter tasks will evaluate candidate processing functions and representational capacities thought to enable episodic memory: 1) the contribution of recollection and familiarity to visual recognition, 2) the temporal organization of memory, 3) memory for the context in which events occur, and 4) the relational organization of memory. By defining the specific nature of age-related memory impairment, the aim is to establish an optimally sensitive framework for relating functional decline to underlying neurobiological and endocrine changes. Toward this end, behaviorally characterized monkeys will receive annual structural magnetic resonance imaging (MRI) and positron emission tomography (PET) scans with the goal of testing several targeted hypotheses about the integrity of neural systems critical for normal memory, in close temporal contiguity with behavioral assessment. The results will also be evaluated by exploratory SPM analysis, suited to revealing unanticipated regions of age-related metabolic change. Continuing a long-standing theme of the project, menses activity and ovarian hormone profiles will be documented regularly for all subjects over the course of the experiments. By this integrated, multidisciplinary approach, the overall aim is to establish a unified account of the critical relationships between cognitive, neurobioological and endocrine consequences of normal aging in primates.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG010606-16
Application #
7837709
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Wagster, Molly V
Project Start
1992-09-20
Project End
2012-04-30
Budget Start
2010-05-01
Budget End
2012-04-30
Support Year
16
Fiscal Year
2010
Total Cost
$455,004
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Neurosciences
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
Hara, Yuko; Yuk, Frank; Puri, Rishi et al. (2016) Estrogen Restores Multisynaptic Boutons in the Dorsolateral Prefrontal Cortex while Promoting Working Memory in Aged Rhesus Monkeys. J Neurosci 36:901-10
Young, M E; Ohm, D T; Dumitriu, D et al. (2014) Differential effects of aging on dendritic spines in visual cortex and prefrontal cortex of the rhesus monkey. Neuroscience 274:33-43
Hara, Yuko; Yuk, Frank; Puri, Rishi et al. (2014) Presynaptic mitochondrial morphology in monkey prefrontal cortex correlates with working memory and is improved with estrogen treatment. Proc Natl Acad Sci U S A 111:486-91
Ohm, Daniel T; Bloss, Erik B; Janssen, William G et al. (2012) Clinically relevant hormone treatments fail to induce spinogenesis in prefrontal cortex of aged female rhesus monkeys. J Neurosci 32:11700-5
Hara, Yuko; Rapp, Peter R; Morrison, John H (2012) Neuronal and morphological bases of cognitive decline in aged rhesus monkeys. Age (Dordr) 34:1051-73
Morrison, John H; Baxter, Mark G (2012) The ageing cortical synapse: hallmarks and implications for cognitive decline. Nat Rev Neurosci 13:240-50
Dumitriu, Dani; Berger, Seth I; Hamo, Carine et al. (2012) Vamping: stereology-based automated quantification of fluorescent puncta size and density. J Neurosci Methods 209:97-105
Hara, Yuko; Punsoni, Michael; Yuk, Frank et al. (2012) Synaptic distributions of GluA2 and PKM? in the monkey dentate gyrus and their relationships with aging and memory. J Neurosci 32:7336-44
Shamy, Jul Lea; Habeck, Christian; Hof, Patrick R et al. (2011) Volumetric correlates of spatiotemporal working and recognition memory impairment in aged rhesus monkeys. Cereb Cortex 21:1559-73
Bailey, M E; Wang, A C J; Hao, J et al. (2011) Interactive effects of age and estrogen on cortical neurons: implications for cognitive aging. Neuroscience 191:148-58

Showing the most recent 10 out of 29 publications