Neuronal and morphological bases of cognitive decline in aged rhesus monkeys

Springer Science and Business Media LLC - Tập 34 Số 5 - Trang 1051-1073 - 2012
Yuko Hara1, Peter R. Rapp2, John H. Morrison3
1Fishberg Department of Neuroscience and Kastor Neurobiology of Aging Laboratories, Mount Sinai School of Medicine, New York, NY, 10029, USA
2Laboratory of Experimental Gerontology, National Institute on Aging, Baltimore, MD 21224, USA
3Friedman Brain Institute, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1065, New York, NY, 10029, USA

Tóm tắt

Từ khóa


Tài liệu tham khảo

Aizawa K, Ageyama N, Yokoyama C, Hisatsune T (2009) Age-dependent alteration in hippocampal neurogenesis correlates with learning performance of macaque monkeys. Exp Anim 58(4):403–407

Aizawa K, Ageyama N, Terao K, Hisatsune T (2011) Primate-specific alterations in neural stem/progenitor cells in the aged hippocampus. Neurobiol Aging 32(1):140–150. doi: 10.1016/j.neurobiolaging.2008.12.011

Alvarez P, Zola-Morgan S, Squire LR (1995) Damage limited to the hippocampal region produces long-lasting memory impairment in monkeys. J Neurosci 15(5 Pt 2):3796–3807

Amaral DG (1993) Morphological analyses of the brains of behaviorally characterized aged nonhuman primates. Neurobiol Aging 14(6):671–672

Aoki C, Venkatesan C, Go CG, Forman R, Kurose H (1998) Cellular and subcellular sites for noradrenergic action in the monkey dorsolateral prefrontal cortex as revealed by the immunocytochemical localization of noradrenergic receptors and axons. Cereb Cortex 8(3):269–277

Arnsten AF (2006) Fundamentals of attention-deficit/hyperactivity disorder: circuits and pathways. J Clin Psychiatry 67(Suppl 8):7–12

Arnsten AF, Contant TA (1992) Alpha-2 adrenergic agonists decrease distractibility in aged monkeys performing the delayed response task. Psychopharmacology (Berl) 108(1–2):159–169

Arnsten AF, Goldman-Rakic PS (1985) Alpha 2-adrenergic mechanisms in prefrontal cortex associated with cognitive decline in aged nonhuman primates. Science 230(4731):1273–1276

Arnsten AF, Goldman-Rakic PS (1990) Analysis of alpha-2 adrenergic agonist effects on the delayed nonmatch-to-sample performance of aged rhesus monkeys. Neurobiol Aging 11(6):583–590

Arnsten AF, Li BM (2005) Neurobiology of executive functions: catecholamine influences on prefrontal cortical functions. Biol Psychiatry 57(11):1377–1384. doi: 10.1016/j.biopsych.2004.08.019

Arnsten AF, Cai JX, Murphy BL, Goldman-Rakic PS (1994) Dopamine D1 receptor mechanisms in the cognitive performance of young adult and aged monkeys. Psychopharmacology (Berl) 116(2):143–151

Arnsten AF, Steere JC, Jentsch DJ, Li BM (1998) Noradrenergic influences on prefrontal cortical cognitive function: opposing actions at postjunctional alpha 1 versus alpha 2-adrenergic receptors. Adv Pharmacol 42:764–767

Bachevalier J, Mishkin M (1986) Visual recognition impairment follows ventromedial but not dorsolateral prefrontal lesions in monkeys. Behav Brain Res 20(3):249–261

Bachevalier J, Landis LS, Walker LC, Brickson M, Mishkin M, Price DL, Cork LC (1991) Aged monkeys exhibit behavioral deficits indicative of widespread cerebral dysfunction. Neurobiol Aging 12(2):99–111

Bai L, Hof PR, Standaert DG, Xing Y, Nelson SE, Young AB, Magnusson KR (2004) Changes in the expression of the NR2B subunit during aging in macaque monkeys. Neurobiol Aging 25(2):201–208

Barbas H, Rempel-Clower N (1997) Cortical structure predicts the pattern of corticocortical connections. Cereb Cortex 7(7):635–646

Bartus RT, Fleming D, Johnson HR (1978) Aging in the rhesus monkey: debilitating effects on short-term memory. J Gerontol 33(6):858–871

Bartus RT, Dean RL 3rd, Fleming DL (1979) Aging in the rhesus monkey: effects on visual discrimination learning and reversal learning. J Gerontol 34(2):209–219

Beal MF, Walker LC, Storey E, Segar L, Price DL, Cork LC (1991) Neurotransmitters in neocortex of aged rhesus monkeys. Neurobiol Aging 12(5):407–412

Beason-Held LL, Rosene DL, Killiany RJ, Moss MB (1999) Hippocampal formation lesions produce memory impairment in the rhesus monkey. Hippocampus 9(5):562–574. doi: 10.1002/(SICI)1098-1063(1999)9:5<562::AID-HIPO10>3.0.CO;2-X

Bigham MH, Lidow MS (1995) Adrenergic and serotonergic receptors in aged monkey neocortex. Neurobiol Aging 16(1):91–104

Bliss TV, Collingridge GL (1993) A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361(6407):31–39. doi: 10.1038/361031a0

Brozoski TJ, Brown RM, Rosvold HE, Goldman PS (1979) Cognitive deficit caused by regional depletion of dopamine in prefrontal cortex of rhesus monkey. Science 205(4409):929–932

Buckmaster CA, Eichenbaum H, Amaral DG, Suzuki WA, Rapp PR (2004) Entorhinal cortex lesions disrupt the relational organization of memory in monkeys. J Neurosci 24(44):9811–9825. doi: 10.1523/JNEUROSCI.1532-04.2004

Calhoun ME, Mao Y, Roberts JA, Rapp PR (2004) Reduction in hippocampal cholinergic innervation is unrelated to recognition memory impairment in aged rhesus monkeys. J Comp Neurol 475(2):238–246. doi: 10.1002/cne.20181

Carroll RC, Zukin RS (2002) NMDA-receptor trafficking and targeting: implications for synaptic transmission and plasticity. Trends Neurosci 25(11):571–577

Chang YM, Rosene DL, Killiany RJ, Mangiamele LA, Luebke JI (2005) Increased action potential firing rates of layer 2/3 pyramidal cells in the prefrontal cortex are significantly related to cognitive performance in aged monkeys. Cereb Cortex 15(4):409–418. doi: 10.1093/cercor/bhh144

Clarke HF, Dalley JW, Crofts HS, Robbins TW, Roberts AC (2004) Cognitive inflexibility after prefrontal serotonin depletion. Science 304(5672):878–880. doi: 10.1126/science.1094987

Clarke HF, Walker SC, Crofts HS, Dalley JW, Robbins TW, Roberts AC (2005) Prefrontal serotonin depletion affects reversal learning but not attentional set shifting. J Neurosci 25(2):532–538. doi: 10.1523/JNEUROSCI.3690-04.2005

Clarke HF, Walker SC, Dalley JW, Robbins TW, Roberts AC (2007) Cognitive inflexibility after prefrontal serotonin depletion is behaviorally and neurochemically specific. Cereb Cortex 17(1):18–27. doi: 10.1093/cercor/bhj120

Cork LC (1993) Plaques in prefrontal cortex of aged, behaviorally-tested rhesus monkeys: incidence, distribution, and relationship to task performance. Neurobiol Aging 14(6):675–676

Corkin S (1984) Lasting consequences of bilateral medial temporal lobectomy: clinical course and experimental findings in H.M. Semin Neurol 4:249–259

Cruz L, Roe DL, Urbanc B, Cabral H, Stanley HE, Rosene DL (2004) Age-related reduction in microcolumnar structure in area 46 of the rhesus monkey correlates with behavioral decline. Proc Natl Acad Sci USA 101(45):15846–15851. doi: 10.1073/pnas.0407002101

Cupp CJ, Uemura E (1980) Age-related changes in prefrontal cortex of Macaca mulatta: quantitative analysis of dendritic branching patterns. Exp Neurol 69(1):143–163. doi: 10.1016/0014-4886(80)90150-8

Dias R, Robbins TW, Roberts AC (1996) Primate analogue of the Wisconsin Card Sorting Test: effects of excitotoxic lesions of the prefrontal cortex in the marmoset. Behav Neurosci 110(5):872–886

Divac I, Rosvold HE, Szwarcbart MK (1967) Behavioral effects of selective ablation of the caudate nucleus. J Comp Physiol Psychol 63(2):184–190

Duan H, Wearne SL, Rocher AB, Macedo A, Morrison JH, Hof PR (2003) Age-related dendritic and spine changes in corticocortically projecting neurons in macaque monkeys. Cereb Cortex 13(9):950–961

Dumitriu D, Hao J, Hara Y, Kaufmann J, Janssen WG, Lou W, Rapp PR, Morrison JH (2010) Selective changes in thin spine density and morphology in monkey prefrontal cortex correlate with aging-related cognitive impairment. J Neurosci 30(22):7507–7515. doi: 10.1523/JNEUROSCI.6410-09.2010

Eberling JL, Roberts JA, Rapp PR, Tuszynski MH, Jagust WJ (1997) Cerebral glucose metabolism and memory in aged rhesus macaques. Neurobiol Aging 18(4):437–443. doi: 10.1016/S0197-4580(97)00040-7

Fellows LK, Farah MJ (2003) Ventromedial frontal cortex mediates affective shifting in humans: evidence from a reversal learning paradigm. Brain 126(Pt 8):1830–1837. doi: 10.1093/brain/awg180

Friedman HR, Goldman-Rakic PS (1988) Activation of the hippocampus and dentate gyrus by working-memory: a 2-deoxyglucose study of behaving rhesus monkeys. J Neurosci 8(12):4693–4706

Fristoe NM, Salthouse TA, Woodard JL (1997) Examination of age-related deficits on the Wisconsin Card Sorting Test. Neuropsychology 11(3):428–436

Funahashi S, Bruce CJ, Goldman-Rakic PS (1989) Mnemonic coding of visual space in the monkey’s dorsolateral prefrontal cortex. J Neurophysiol 61(2):331–349

Funahashi S, Bruce CJ, Goldman-Rakic PS (1993) Dorsolateral prefrontal lesions and oculomotor delayed-response performance: evidence for mnemonic “scotomas”. J Neurosci 13(4):1479–1497

Gazzaley AH, Siegel SJ, Kordower JH, Mufson EJ, Morrison JH (1996) Circuit-specific alterations of N-methyl-D-aspartate receptor subunit 1 in the dentate gyrus of aged monkeys. Proc Natl Acad Sci USA 93(7):3121–3125

Gazzaley AH, Thakker MM, Hof PR, Morrison JH (1997) Preserved number of entorhinal cortex layer II neurons in aged macaque monkeys. Neurobiol Aging 18(5):549–553

Gearing M, Tigges J, Mori H, Mirra SS (1996) A beta40 is a major form of beta-amyloid in nonhuman primates. Neurobiol Aging 17(6):903–908

Geinisman Y, de Toledo-Morrell L, Morrell F (1986) Aged rats need a preserved complement of perforated axospinous synapses per hippocampal neuron to maintain good spatial memory. Brain Res 398(2):266–275. doi: 10.1016/0006-8993(86)91486-1

Geinisman Y, deToledo-Morrell L, Morrell F (1991) Induction of long-term potentiation is associated with an increase in the number of axospinous synapses with segmented postsynaptic densities. Brain Res 566(1–2):77–88. doi: 10.1016/0006-8993(91)91683-R

Geinisman Y, Berry RW, Disterhoft JF, Power JM, Van der Zee EA (2001) Associative learning elicits the formation of multiple-synapse boutons. J Neurosci 21(15):5568–5573

Gilardi KV, Shideler SE, Valverde CR, Roberts JA, Lasley BL (1997) Characterization of the onset of menopause in the rhesus macaque. Biol Reprod 57(2):335–340

Goldman-Rakic PS (1995) Cellular basis of working memory. Neuron 14(3):477–485. doi: 10.1016/0896-6273(95)90304-6

Goldman-Rakic PS, Brown RM (1981) Regional changes of monoamines in cerebral cortex and subcortical structures of aging rhesus monkeys. Neuroscience 6(2):177–187. doi: 10.1016/0306-4522(81)90053-1

Greenough WT, West RW, DeVoogd TJ (1978) Subsynaptic plate perforations: changes with age and experience in the rat. Science 202(4372):1096–1098

Groc L, Choquet D (2006) AMPA and NMDA glutamate receptor trafficking: multiple roads for reaching and leaving the synapse. Cell Tissue Res 326(2):423–438. doi: 10.1007/s00441-006-0254-9

Haaland KY, Vranes LF, Goodwin JS, Garry PJ (1987) Wisconsin Card Sort Test performance in a healthy elderly population. J Gerontol 42(3):345–346

Hao J, Rapp PR, Janssen WG, Lou W, Lasley BL, Hof PR, Morrison JH (2007) Interactive effects of age and estrogen on cognition and pyramidal neurons in monkey prefrontal cortex. Proc Natl Acad Sci USA 104(27):11465–11470. doi: 10.1073/pnas.0704757104

Hara Y, Park CS, Janssen WG, Roberts MT, Morrison JH, Rapp PR (2010) Synaptic correlates of memory and menopause in the hippocampal dentate gyrus in rhesus monkeys. Neurobiol Aging. doi: 10.1016/j.neurobiolaging.2010.09.014

Hara Y, Park CS, Janssen WG, Punsoni M, Rapp PR, Morrison JH (2011) Synaptic characteristics of dentate gyrus axonal boutons and their relationships with aging, menopause, and memory in female rhesus monkeys. J Neurosci 31(21):7737–7744. doi: 10.1523/JNEUROSCI.0822-11.2011

Harris KM (1995) How multiple-synapse boutons could preserve input specificity during an interneuronal spread of LTP. Trends Neurosci 18(8):365–369

Henderson VW (2008) Cognitive changes after menopause: influence of estrogen. Clin Obstet Gynecol 51(3):618–626. doi: 10.1097/GRF.0b013e318180ba10

Heynen AJ, Quinlan EM, Bae DC, Bear MF (2000) Bidirectional, activity-dependent regulation of glutamate receptors in the adult hippocampus in vivo. Neuron 28(2):527–536. doi: 10.1016/S0896-6273(00)00130-6

Hof PR, Nimchinsky EA, Young WG, Morrison JH (2000) Numbers of Meynert and layer IVB cells in area V1: a stereologic analysis in young and aged macaque monkeys. J Comp Neurol 420(1):113–126. doi: 10.1002/(SICI)1096-9861(20000424)420:1<113::AID-CNE8>3.0.CO;2-N

Hof PR, Duan H, Page TL, Einstein M, Wicinski B, He Y, Erwin JM, Morrison JH (2002) Age-related changes in GluR2 and NMDAR1 glutamate receptor subunit protein immunoreactivity in corticocortically projecting neurons in macaque and patas monkeys. Brain Res 928(1–2):175–186

Inouye SK, Albert MS, Mohs R, Sun K, Berkman LF (1993) Cognitive performance in a high-functioning community-dwelling elderly population. J Gerontol 48(4):M146–M151

Iversen SD, Mishkin M (1970) Perseverative interference in monkeys following selective lesions of the inferior prefrontal convexity. Exp Brain Res 11(4):376–386

Jones TA, Chu CJ, Grande LA, Gregory AD (1999) Motor skills training enhances lesion-induced structural plasticity in the motor cortex of adult rats. J Neurosci 19(22):10153–10163

Kabaso D, Coskren PJ, Henry BI, Hof PR, Wearne SL (2009) The electrotonic structure of pyramidal neurons contributing to prefrontal cortical circuits in macaque monkeys is significantly altered in aging. Cereb Cortex 19(10):2248–2268. doi: 10.1093/cercor/bhn242

Kasai H, Matsuzaki M, Noguchi J, Yasumatsu N, Nakahara H (2003) Structure–stability–function relationships of dendritic spines. Trends Neurosci 26(7):360–368

Kaye JA, Swihart T, Howieson D, Dame A, Moore MM, Karnos T, Camicioli R, Ball M, Oken B, Sexton G (1997) Volume loss of the hippocampus and temporal lobe in healthy elderly persons destined to develop dementia. Neurology 48(5):1297–1304

Kessels HW, Malinow R (2009) Synaptic AMPA receptor plasticity and behavior. Neuron 61(3):340–350. doi: 10.1016/j.neuron.2009.01.015

Keuker JI, Luiten PG, Fuchs E (2003) Preservation of hippocampal neuron numbers in aged rhesus monkeys. Neurobiol Aging 24(1):157–165

Kimura N, Tanemura K, Nakamura S, Takashima A, Ono F, Sakakibara I, Ishii Y, Kyuwa S, Yoshikawa Y (2003) Age-related changes of Alzheimer’s disease-associated proteins in cynomolgus monkey brains. Biochem Biophys Res Commun 310(2):303–311

Kondo H, Lavenex P, Amaral DG (2008) Intrinsic connections of the macaque monkey hippocampal formation: I. Dentate gyrus. J Comp Neurol 511(4):497–520. doi: 10.1002/cne.21825

Lai ZC, Moss MB, Killiany RJ, Rosene DL, Herndon JG (1995) Executive system dysfunction in the aged monkey: spatial and object reversal learning. Neurobiol Aging 16(6):947–954

Lee B, Groman S, London ED, Jentsch JD (2007) Dopamine D2/D3 receptors play a specific role in the reversal of a learned visual discrimination in monkeys. Neuropsychopharmacology 32(10):2125–2134. doi: 10.1038/sj.npp.1301337

Li BM, Mao ZM, Wang M, Mei ZT (1999) Alpha-2 adrenergic modulation of prefrontal cortical neuronal activity related to spatial working memory in monkeys. Neuropsychopharmacology 21(5):601–610. doi: 10.1016/S0893-133X(99)00070-6

Luebke JI, Amatrudo JM (2010) Age-related increase of sI(AHP) in prefrontal pyramidal cells of monkeys: relationship to cognition. Neurobiol Aging. doi: 10.1016/j.neurobiolaging.2010.07.002

Luebke JI, Chang YM (2007) Effects of aging on the electrophysiological properties of layer 5 pyramidal cells in the monkey prefrontal cortex. Neuroscience 150(3):556–562. doi: 10.1016/j.neuroscience.2007.09.042

Luebke JI, Rosene DL (2003) Aging alters dendritic morphology, input resistance, and inhibitory signaling in dentate granule cells of the rhesus monkey. J Comp Neurol 460(4):573–584. doi: 10.1002/cne.10668

Luebke JI, Chang YM, Moore TL, Rosene DL (2004) Normal aging results in decreased synaptic excitation and increased synaptic inhibition of layer 2/3 pyramidal cells in the monkey prefrontal cortex. Neuroscience 125(1):277–288. doi: 10.1016/j.neuroscience.2004.01.035

Luebke J, Barbas H, Peters A (2010) Effects of normal aging on prefrontal area 46 in the rhesus monkey. Brain Res Rev 62(2):212–232. doi: 10.1016/j.brainresrev.2009.12.002

Makris N, Kennedy DN, Boriel DL, Rosene DL (2010) Methods of MRI-based structural imaging in the aging monkey. Methods 50(3):166–177. doi: 10.1016/j.ymeth.2009.06.007

McEnaney KW, Butter CM (1969) Perseveration of responding and nonresponding in monkeys with orbital frontal ablations. J Comp Physiol Psychol 68(4):558–561

Merrill DA, Roberts JA, Tuszynski MH (2000) Conservation of neuron number and size in entorhinal cortex layers II, III, and V/VI of aged primates. J Comp Neurol 422(3):396–401. doi: 10.1002/1096-9861(20000703)422:3<396::AID-CNE6>3.0.CO;2-R

Mesulam MM, Mufson EJ, Levey AI, Wainer BH (1983) Cholinergic innervation of cortex by the basal forebrain: cytochemistry and cortical connections of the septal area, diagonal band nuclei, nucleus basalis (substantia innominata), and hypothalamus in the rhesus monkey. J Comp Neurol 214(2):170–197. doi: 10.1002/cne.902140206

Moore TL, Schettler SP, Killiany RJ, Herndon JG, Luebke JI, Moss MB, Rosene DL (2005) Cognitive impairment in aged rhesus monkeys associated with monoamine receptors in the prefrontal cortex. Behav Brain Res 160(2):208–221. doi: 10.1016/j.bbr.2004.12.003

Moore TL, Killiany RJ, Herndon JG, Rosene DL, Moss MB (2006) Executive system dysfunction occurs as early as middle-age in the rhesus monkey. Neurobiol Aging 27(10):1484–1493. doi: 10.1016/j.neurobiolaging.2005.08.004

Morrison JH, Hof PR (1997) Life and death of neurons in the aging brain. Science 278(5337):412–419

Moss MB, Albert MS, Butters N, Payne M (1986) Differential patterns of memory loss among patients with Alzheimer’s disease, Huntington’s disease, and alcoholic Korsakoff’s syndrome. Arch Neurol 43(3):239–246

Moss MB, Rosene DL, Peters A (1988) Effects of aging on visual recognition memory in the rhesus monkey. Neurobiol Aging 9(5–6):495–502

Moss MB, Killiany RJ, Lai ZC, Rosene DL, Herndon JG (1997) Recognition memory span in rhesus monkeys of advanced age. Neurobiol Aging 18(1):13–19

Mountcastle VB (2003) Introduction. Computation in cortical columns. Cereb Cortex 13(1):2–4

Mueller EA, Moore MM, Kerr DC, Sexton G, Camicioli RM, Howieson DB, Quinn JF, Kaye JA (1998) Brain volume preserved in healthy elderly through the eleventh decade. Neurology 51(6):1555–1562

Murray EA, Mishkin M (1998) Object recognition and location memory in monkeys with excitotoxic lesions of the amygdala and hippocampus. J Neurosci 18(16):6568–6582

Nagahara AH, Bernot T, Tuszynski MH (2010) Age-related cognitive deficits in rhesus monkeys mirror human deficits on an automated test battery. Neurobiol Aging 31(6):1020–1031. doi: 10.1016/j.neurobiolaging.2008.07.007

Nusser Z, Lujan R, Laube G, Roberts JD, Molnar E, Somogyi P (1998) Cell type and pathway dependence of synaptic AMPA receptor number and variability in the hippocampus. Neuron 21(3):545–559. doi: 10.1016/S0896-6273(00)80565-6

O’Donnell KA, Rapp PR, Hof PR (1999) Preservation of prefrontal cortical volume in behaviorally characterized aged macaque monkeys. Exp Neurol 160(1):300–310. doi: 10.1006/exnr.1999.7192

Peters A, Kaiserman-Abramof IR (1969) The small pyramidal neuron of the rat cerebral cortex. The synapses upon dendritic spines. Z Zellforsch Mikrosk Anat 100(4):487–506

Peters A, Sethares C (2002) The effects of age on the cells in layer 1 of primate cerebral cortex. Cereb Cortex 12(1):27–36

Peters A, Leahu D, Moss MB, McNally KJ (1994) The effects of aging on area 46 of the frontal cortex of the rhesus monkey. Cereb Cortex 4(6):621–635

Peters A, Rosene DL, Moss MB, Kemper TL, Abraham CR, Tigges J, Albert MS (1996) Neurobiological bases of age-related cognitive decline in the rhesus monkey. J Neuropathol Exp Neurol 55(8):861–874

Peters A, Morrison JH, Rosene DL, Hyman BT (1998a) Feature article: are neurons lost from the primate cerebral cortex during normal aging? Cereb Cortex 8(4):295–300

Peters A, Sethares C, Moss MB (1998b) The effects of aging on layer 1 in area 46 of prefrontal cortex in the rhesus monkey. Cereb Cortex 8(8):671–684

Peters A, Jones EG, Morrison JH (1999) Cerebral cortex: neurodegenerative and age-related changes in structure and function of cerebral cortex, vol 14. Springer, New York

Peters A, Moss MB, Sethares C (2001) The effects of aging on layer 1 of primary visual cortex in the rhesus monkey. Cereb Cortex 11(2):93–103

Peters A, Sethares C, Luebke JI (2008) Synapses are lost during aging in the primate prefrontal cortex. Neuroscience 152(4):970–981. doi: 10.1016/j.neuroscience.2007.07.014

Petrides M, Pandya DN (1999) Dorsolateral prefrontal cortex: comparative cytoarchitectonic analysis in the human and the macaque brain and corticocortical connection patterns. Eur J Neurosci 11(3):1011–1036

Porrino LJ, Goldman-Rakic PS (1982) Brainstem innervation of prefrontal and anterior cingulate cortex in the rhesus monkey revealed by retrograde transport of HRP. J Comp Neurol 205(1):63–76. doi: 10.1002/cne.902050107

Presty SK, Bachevalier J, Walker LC, Struble RG, Price DL, Mishkin M, Cork LC (1987) Age differences in recognition memory of the rhesus monkey (Macaca mulatta). Neurobiol Aging 8(5):435–440

Price JL, Ko AI, Wade MJ, Tsou SK, McKeel DW, Morris JC (2001) Neuron number in the entorhinal cortex and CA1 in preclinical Alzheimer disease. Arch Neurol 58(9):1395–1402

Rapp PR (1990) Visual discrimination and reversal learning in the aged monkey (Macaca mulatta). Behav Neurosci 104(6):876–884

Rapp PR (1995) Emotion, memory and behavior: studies on human and nonhuman primates, vol 18. Cognitive neuroscience perspectives on aging in nonhuman primates. Japan Scientific Societies, Tokyo

Rapp PR, Amaral DG (1989) Evidence for task-dependent memory dysfunction in the aged monkey. J Neurosci 9(10):3568–3576

Rapp PR, Amaral DG (1991) Recognition memory deficits in a subpopulation of aged monkeys resemble the effects of medial temporal lobe damage. Neurobiol Aging 12(5):481–486

Rapp PR, Morrison JH, Roberts JA (2003) Cyclic estrogen replacement improves cognitive function in aged ovariectomized rhesus monkeys. J Neurosci 23(13):5708–5714

Raz N, Rodrigue KM, Head D, Kennedy KM, Acker JD (2004) Differential aging of the medial temporal lobe: a study of a five-year change. Neurology 62(3):433–438

Rhodes MG (2004) Age-related differences in performance on the Wisconsin Card Sorting Test: a meta-analytic review. Psychol Aging 19(3):482–494. doi: 10.1037/0882-7974.19.3.482

Roberts JA, Gilardi KV, Lasley B, Rapp PR (1997) Reproductive senescence predicts cognitive decline in aged female monkeys. Neuroreport 8(8):2047–2051

Rogers RD, Andrews TC, Grasby PM, Brooks DJ, Robbins TW (2000) Contrasting cortical and subcortical activations produced by attentional-set shifting and reversal learning in humans. J Cogn Neurosci 12(1):142–162

Saper CB (1984) Organization of cerebral cortical afferent systems in the rat. II. Magnocellular basal nucleus. J Comp Neurol 222(3):313–342. doi: 10.1002/cne.902220302

Scheff SW, Price DA, Sparks DL (2001) Quantitative assessment of possible age-related change in synaptic numbers in the human frontal cortex. Neurobiol Aging 22(3):355–365

Shamy JL, Buonocore MH, Makaron LM, Amaral DG, Barnes CA, Rapp PR (2006) Hippocampal volume is preserved and fails to predict recognition memory impairment in aged rhesus monkeys (Macaca mulatta). Neurobiol Aging 27(10):1405–1415. doi: 10.1016/j.neurobiolaging.2005.07.019

Shamy JL, Habeck C, Hof PR, Amaral DG, Fong SG, Buonocore MH, Stern Y, Barnes CA, Rapp PR (2010) Volumetric correlates of spatiotemporal working and recognition memory impairment in aged rhesus monkeys. Cereb Cortex. doi: 10.1093/cercor/bhq210

Simic G, Kostovic I, Winblad B, Bogdanovic N (1997) Volume and number of neurons of the human hippocampal formation in normal aging and Alzheimer’s disease. J Comp Neurol 379(4):482–494. doi: 10.1002/(SICI)1096-9861(19970324)379:4<482::AID-CNE2>3.0.CO;2-Z

Sloane JA, Pietropaolo MF, Rosene DL, Moss MB, Peters A, Kemper T, Abraham CR (1997) Lack of correlation between plaque burden and cognition in the aged monkey. Acta Neuropathol 94(5):471–478

Small SA, Chawla MK, Buonocore M, Rapp PR, Barnes CA (2004) Imaging correlates of brain function in monkeys and rats isolates a hippocampal subregion differentially vulnerable to aging. Proc Natl Acad Sci USA 101(18):7181–7186. doi: 10.1073/pnas.0400285101

Smith DE, Rapp PR, McKay HM, Roberts JA, Tuszynski MH (2004) Memory impairment in aged primates is associated with focal death of cortical neurons and atrophy of subcortical neurons. J Neurosci 24(18):4373–4381. doi: 10.1523/JNEUROSCI.4289-03.2004

Soghomonian JJ, Sethares C, Peters A (2010) Effects of age on axon terminals forming axosomatic and axodendritic inhibitory synapses in prefrontal cortex. Neuroscience 168(1):74–81. doi: 10.1016/j.neuroscience.2010.03.020

Spencer JL, Waters EM, Romeo RD, Wood GE, Milner TA, McEwen BS (2008) Uncovering the mechanisms of estrogen effects on hippocampal function. Front Neuroendocrinol 29(2):219–237. doi: 10.1016/j.yfrne.2007.08.006

Squire LR, Zola-Morgan S (1988) Memory: brain systems and behavior. Trends Neurosci 11(4):170–175. doi: 10.1016/0166-2236(88)90144-0

Squire LR, Zola-Morgan S, Chen KS (1988) Human amnesia and animal models of amnesia: performance of amnesic patients on tests designed for the monkey. Behav Neurosci 102(2):210–221

Steere JC, Arnsten AF (1997) The alpha-2A noradrenergic receptor agonist guanfacine improves visual object discrimination reversal performance in aged rhesus monkeys. Behav Neurosci 111(5):883–891

Sterio DC (1984) The unbiased estimation of number and sizes of arbitrary particles using the disector. J Microsc 134(Pt 2):127–136

Stroessner-Johnson HM, Rapp PR, Amaral DG (1992) Cholinergic cell loss and hypertrophy in the medial septal nucleus of the behaviorally characterized aged rhesus monkey. J Neurosci 12(5):1936–1944

Tigges J, Gordon TP, McClure HM, Hall EC, Peters A (1988) Survival rate and life span of rhesus monkeys at the Yerkes regional primate research center. Am J Primatol 15:263–273

Tigges J, Herndon JG, Rosene DL (1995) Mild age-related changes in the dentate gyrus of adult rhesus monkeys. Acta Anat (Basel) 153(1):39–48

Tigges J, Herndon JG, Rosene DL (1996) Preservation into old age of synaptic number and size in the supragranular layer of the dentate gyrus in rhesus monkeys. Acta Anat (Basel) 157(1):63–72

Tisserand DJ, Visser PJ, van Boxtel MP, Jolles J (2000) The relation between global and limbic brain volumes on MRI and cognitive performance in healthy individuals across the age range. Neurobiol Aging 21(4):569–576

Toni N, Buchs PA, Nikonenko I, Bron CR, Muller D (1999) LTP promotes formation of multiple spine synapses between a single axon terminal and a dendrite. Nature 402(6760):421–425. doi: 10.1038/46574

Toni N, Buchs PA, Nikonenko I, Povilaitite P, Parisi L, Muller D (2001) Remodeling of synaptic membranes after induction of long-term potentiation. J Neurosci 21(16):6245–6251

Uemura E (1980) Age-related changes in prefrontal cortex of Macaca mulatta: synaptic density. Exp Neurol 69(1):164–172. doi: 10.1016/0014-4886(80)90151-X

Uemura E (1985a) Age-related changes in the subiculum of Macaca mulatta: dendritic branching pattern. Exp Neurol 87(3):412–427

Uemura E (1985b) Age-related changes in the subiculum of Macaca mulatta: synaptic density. Exp Neurol 87(3):403–411

Vijayraghavan S, Wang M, Birnbaum SG, Williams GV, Arnsten AF (2007) Inverted-U dopamine D1 receptor actions on prefrontal neurons engaged in working memory. Nat Neurosci 10(3):376–384. doi: 10.1038/nn1846

Voytko ML (1999) Impairments in acquisition and reversals of two-choice discriminations by aged rhesus monkeys. Neurobiol Aging 20(6):617–627. doi: 10.1016/S0197-4580(99)00097-4

Voytko ML, Tinkler GP (2004) Cognitive function and its neural mechanisms in nonhuman primate models of aging, Alzheimer disease, and menopause. Front Biosci 9:1899–1914

Voytko ML, Sukhov RR, Walker LC, Breckler SJ, Price DL, Koliatsos VE (1995) Neuronal number and size are preserved in the nucleus basalis of aged rhesus monkeys. Dementia 6(3):131–141

Voytko ML, Murray R, Higgs CJ (2009) Executive function and attention are preserved in older surgically menopausal monkeys receiving estrogen or estrogen plus progesterone. J Neurosci 29(33):10362–10370. doi: 10.1523/JNEUROSCI.1591-09.2009

Walhovd KB, Westlye LT, Amlien I, Espeseth T, Reinvang I, Raz N, Agartz I, Salat DH, Greve DN, Fischl B, Dale AM, Fjell AM (2009) Consistent neuroanatomical age-related volume differences across multiple samples. Neurobiol Aging. doi: 10.1016/j.neurobiolaging.2009.05.013

Walker ML, Herndon JG (2008) Menopause in nonhuman primates? Biol Reprod 79(3):398–406. doi: 10.1095/biolreprod.108.068536

Wang AC, Hara Y, Janssen WG, Rapp PR, Morrison JH (2010) Synaptic estrogen receptor-alpha levels in prefrontal cortex in female rhesus monkeys and their correlation with cognitive performance. J Neurosci 30(38):12770–12776. doi: 10.1523/JNEUROSCI.3192-10.2010

Wenk GL, Pierce DJ, Struble RG, Price DL, Cork LC (1989) Age-related changes in multiple neurotransmitter systems in the monkey brain. Neurobiol Aging 10(1):11–19

West MJ (1993) Regionally specific loss of neurons in the aging human hippocampus. Neurobiol Aging 14(4):287–293

West MJ, Amaral DG, Rapp PR (1993) Preserved hippocampal cell number in aged monkeys with recognition memory deficits. Soc for Neurosci Abstr 19:599

Witter MP, Van Hoesen GW, Amaral DG (1989) Topographical organization of the entorhinal projection to the dentate gyrus of the monkey. J Neurosci 9(1):216–228

Woolley CS, McEwen BS (1994) Estradiol regulates hippocampal dendritic spine density via an N-methyl-D-aspartate receptor-dependent mechanism. J Neurosci 14(12):7680–7687

Yankova M, Hart SA, Woolley CS (2001) Estrogen increases synaptic connectivity between single presynaptic inputs and multiple postsynaptic CA1 pyramidal cells: a serial electron-microscopic study. Proc Natl Acad Sci USA 98(6):3525–3530. doi: 10.1073/pnas.051624598

Yassa MA, Muftuler LT, Stark CE (2010) Ultrahigh-resolution microstructural diffusion tensor imaging reveals perforant path degradation in aged humans in vivo. Proc Natl Acad Sci USA 107(28):12687–12691. doi: 10.1073/pnas.1002113107

Zola-Morgan S, Squire LR (1985) Medial temporal lesions in monkeys impair memory on a variety of tasks sensitive to human amnesia. Behav Neurosci 99(1):22–34

Zola-Morgan S, Squire LR, Amaral DG (1986) Human amnesia and the medial temporal region: enduring memory impairment following a bilateral lesion limited to field CA1 of the hippocampus. J Neurosci 6(10):2950–2967

Zola-Morgan S, Squire LR, Amaral DG, Suzuki WA (1989) Lesions of perirhinal and parahippocampal cortex that spare the amygdala and hippocampal formation produce severe memory impairment. J Neurosci 9(12):4355–4370

Zola-Morgan S, Squire LR, Clower RP, Rempel NL (1993) Damage to the perirhinal cortex exacerbates memory impairment following lesions to the hippocampal formation. J Neurosci 13(1):251–265

Zola-Morgan S, Squire LR, Ramus SJ (1994) Severity of memory impairment in monkeys as a function of locus and extent of damage within the medial temporal lobe memory system. Hippocampus 4(4):483–495. doi: 10.1002/hipo.450040410