Our research programs involving awake behaving nonhuman primates are based at the NIH Animal Center (NIHAC) in Poolesville, MD, approximately 90 minutes from most of the NIA laboratories in Baltimore. The NIHAC provides outstanding infrastructure for animal housing, conditioning and quarantine, servicing much of the larger NIH community. The facility is less ideally configured in support of investigator research programs, however, and given the relatively remote location of the Center, opportunities for recruiting and retaining scientific staff can be challenging. Although project start-up has been protracted as a consequence, we have recently recruited a Biologist with significant experience at the NIHAC who we anticipate will substantially facilitate progress. Key project infrastructure has also been established, including custom-designed operant chambers for computer-aided, touch screen based neuropsychological testing, and we continue to retain off-site computer programming expertise in support of this element of the project. Although accessing the outstanding in vivo brain imaging facilities on NIH main campus presents a number of logistical hurdles and administrative issues surrounding reimbursement, we are actively pursuing options for continuing and extending this component of our nonhuman primate research program. Progress from imaging we conducted elsewhere includes a recent study testing whether age-related decline in spatiotemporal and recognition memory is coupled with atrophy of memory-related brain regions in rhesus monkeys (Shamy et al., 2011). Key findings were that, in contrast to expectations derived from lesion and electrophysiological studies in young subjects, the volume of selected prefrontal cortex (PFC) areas was coupled with the status of memory that is typically considered an exemplar of medial temporal lobe function. Hippocampal volume, by comparison, predicted performance on a classic test of PFC integrity (the delayed response task). Together, the results provide novel support for the view that cognitive aging in primates arises from region-specific morphometric alterations that are distributed across multiple memory-related brain systems, prominently including subdivisions of the PFC (Shamy et al, 2011). Complementing the overall project aims, collaborative studies have also examined individual differences in the neurocognitive outcome of aging in rhesus monkeys in relation to naturally occurring ovarian hormone decline. In two recently published reports, for example, brain material from behaviorally characterized young and aged subjects was used to evaluate synaptic density and morphology in the hippocampal dentate gyrus by quantitative electron microscopy (Hara et al., 2010;2011). These findings, together with observations from our related studies of surgical menopause and hormone treatment in monkeys, make the important point that the aged primate hippocampus remains sensitive to ovarian hormone status, and that the influence of reproductive senescence on circuit-specific synaptic subtypes may contribute to the effects of aging on hippocampal memory function. Progress in this area of research is surveyed in a number of recent reviews (e.g., Hara et al., 2011;Dumitriu et al., 2010).

National Institute of Health (NIH)
National Institute on Aging (NIA)
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National Institute on Aging
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Kyle, Colin T; Permenter, Michele R; Vogt, Julie A et al. (2018) Behavioral Impact of Long-Term Chronic Implantation of Neural Recording Devices in the Rhesus Macaque. Neuromodulation :
Crimins, Johanna L; Wang, Athena Ching-Jung; Yuk, Frank et al. (2017) Diverse Synaptic Distributions of G Protein-coupled Estrogen Receptor 1 in Monkey Prefrontal Cortex with Aging and Menopause. Cereb Cortex 27:2022-2033
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
Kim, Wook; Fiori, Jennifer L; Shin, Yu-Kyong et al. (2014) Pancreatic polypeptide inhibits somatostatin secretion. FEBS Lett 588:3233-9
Ash, Jessica A; Rapp, Peter R (2014) A quantitative neural network approach to understanding aging phenotypes. Ageing Res Rev 15:44-50
Naugle, Michelle M; Nguyen, Long T; Merceron, Tyler K et al. (2014) G-protein coupled estrogen receptor, estrogen receptor ?, and progesterone receptor immunohistochemistry in the hypothalamus of aging female rhesus macaques given long-term estradiol treatment. J Exp Zool A Ecol Genet Physiol 321:399-414
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
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
Hara, Yuko; Park, C Sehwan; Janssen, William G M et al. (2012) Synaptic correlates of memory and menopause in the hippocampal dentate gyrus in rhesus monkeys. Neurobiol Aging 33:421.e17-28

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