Impact of aging on hippocampal function: plasticity, network dynamics, and cognition

Progress in Neurobiology - Tập 69 - Trang 143-179 - 2003
Ephron S Rosenzweig1, Carol A Barnes1,2,3
1Arizona Research Laboratories Division of Neural Systems, Memory and Aging, University of Arizona, Tucson, AZ, USA
2Department of Psychology, University of Arizona, Tucson, AZ, USA
3Department of Neurology, University of Arizona, Tucson, AZ, USA

Tài liệu tham khảo

Abbott, 1996, Functional significance of long-term potentiation for sequence learning and prediction, Cereb. Cortex, 6, 406, 10.1093/cercor/6.3.406 Abdulla, 1995, Importance of forebrain cholinergic and GABAergic systems to the age-related deficits in water maze performance of rats, Neurobiol. Aging, 16, 41, 10.1016/0197-4580(95)80006-D Abel, 1997, Genetic demonstration of a role for PKA in the late phase of LTP and in hippocampus-based long-term memory, Cell, 88, 615, 10.1016/S0092-8674(00)81904-2 Abraham, 1996, Metaplasticity: the plasticity of synaptic plasticity, Trends Neurosci., 19, 126, 10.1016/S0166-2236(96)80018-X Abraham, 1997, Metaplasticity: a new vista across the field of synaptic plasticity, Prog. Neurobiol., 52, 303, 10.1016/S0301-0082(97)00018-X Abraham, 2001, Heterosynaptic metaplasticity in the hippocampus in vivo: a BCM-like modifiable threshold for LTP, Proc. Natl. Acad. Sci. U.S.A., 98, 10924, 10.1073/pnas.181342098 Abrous, 1997, Decrease in highly polysialylated neuronal cell adhesion molecules and in spatial learning during ageing are not correlated, Brain Res., 744, 285, 10.1016/S0006-8993(96)01115-8 Adams, 2001, Hippocampal dependent learning ability correlates with N-methyl-d-aspartate (NMDA) receptor levels in CA3 neurons of young and aged rats, J. Comp. Neurol., 432, 230, 10.1002/cne.1099 Aitken, 1989, Temporally graded, age-related impairments in spatial memory in the rat, Neurobiol. Aging, 10, 273, 10.1016/0197-4580(89)90062-6 Alyan, 1999, Hippocampectomized rats are capable of homing by path integration, Behav. Neurosci., 113, 19, 10.1037/0735-7044.113.1.19 Amamoto, 1999, Relationship between hippocampal arachidonic acid content and induction of LTP in aged rats (in Japanese), Nihon Shinkei Seishin Yakurigaku Zasshi, 19, 273 Andersen, P., Lomo, T., 1967. Control of hippocampal output by afferent volley frequency. In: Adey, W.R., Tokizane, T. (Eds.), Structure and Function of the Limbic System: Progress in Brain Research, vol. 27. Elsevier, Amsterdam, pp. 400–413. Aniksztejn, 1991, Novel form of long-term potentiation produced by K+ channel blocker in the hippocampus, Nature, 349, 67, 10.1038/349067a0 Anwyl, 1999, Metabotropic glutamate receptors: electrophysiological properties and role in plasticity, Brain Res. Brain Res. Rev., 29, 83, 10.1016/S0165-0173(98)00050-2 Applegate, 1988, Synaptic vesicle redistribution during hippocampal frequency potentiation and depression in young and aged rats, J. Neurosci., 8, 1096, 10.1523/JNEUROSCI.08-04-01096.1988 Applegate, 1984, Reorganization of ultrastructure in aging rat hippocampus: a stereological analysis, Soc. Neurosci. Abstr., 10, 450 Artola, 1993, Long-term depression of excitatory synaptic transmission and its relationship to long-term potentiation, Trends Neurosci., 16, 480, 10.1016/0166-2236(93)90081-V Asanuma, 1996, Alterations of cAMP response element-binding activity in the aged rat brain in response to administration of rolipram, a cAMP-specific phosphodiesterase inhibitor, Brain Res. Mol. Brain Res., 41, 210, 10.1016/0169-328X(96)00098-8 Bach, 1995, Impairment of spatial but not contextual memory in CaMKII mutant mice with a selection loss of hippocampal LTP in the range of the theta frequency, Cell, 81, 905, 10.1016/0092-8674(95)90010-1 Bach, 1999, Age-related defects in spatial memory are correlated with defects in the late phase of hippocampal long-term potentiation in vitro and are attenuated by drugs that enhance the cAMP signaling pathway, Proc. Natl. Acad. Sci. U.S.A., 96, 5280, 10.1073/pnas.96.9.5280 Bäckman, 1996, Systemic administration of a nerve growth factor conjugate reverses age-related cognitive dysfunction and prevents cholinergic neuron atrophy, J. Neurosci., 16, 5437, 10.1523/JNEUROSCI.16-17-05437.1996 Backman, L., Small, B.J., Wahlin, A., 2001. Aging and memory: cognitive and biological perspectives. In: Birren, J.E., Schaie, K.W. (Eds.), Handbook of the Psychology of Aging. Academic Press, San Diego, pp. 349–377. Badiali de Giorgi, 1987, Ultrastructural aspects of ageing rat hippocampus and effects of l-acetyl-carnitine treatment, Drugs Exp. Clin. Res., 13, 185 Banke, 2000, Control of GluR1 AMPA receptor function by cAMP-dependent protein kinase, J. Neurosci., 20, 89, 10.1523/JNEUROSCI.20-01-00089.2000 Bannerman, 1995, Distinct components of spatial learning revealed by prior training and NMDA receptor blockade, Nature, 378, 182, 10.1038/378182a0 Barad, 1998, Rolipram, a type IV-specific phosphodiesterase inhibitor, facilitates the establishment of long-lasting long-term potentiation and improves memory, Proc. Natl. Acad. Sci. U.S.A., 95, 15020, 10.1073/pnas.95.25.15020 Barnes, 1979, Memory deficits associated with senescence: a neurophysiological and behavioral study in the rat, J. Comp. Physiol. Psychol., 93, 74, 10.1037/h0077579 Barnes, 1988, Aging and the physiology of spatial memory, Neurobiol. Aging, 9, 563, 10.1016/S0197-4580(88)80114-3 Barnes, C.A., 1990. Animal models of age-related cognitive decline. In: Boller, F., Grafman, J. (Eds.), Handbook of Neuropsychology. Elsevier, Amsterdam, pp. 169–196. Barnes, 1994, Normal aging: regionally specific changes in hippocampal synaptic transmission, Trends Neurosci., 17, 13, 10.1016/0166-2236(94)90029-9 Barnes, 1999, Do synaptic markers provide a window on synaptic effectiveness in the aged hippocampus?, Neurobiol. Aging, 20, 349 Barnes, 1979, Neurophysiological comparison of dendritic cable properties in adolescent, middle-aged, and senescent rats, Exp. Brain Res., 5, 195 Barnes, 1980, Physiological compensation for loss of afferent synapses in rat hippocampal granule cells during senescence, J. Physiol. (London), 309, 473, 10.1113/jphysiol.1980.sp013521 Barnes, C.A., McNaughton, B.L., 1980b. Spatial memory and hippocampal synaptic plasticity in middle-aged and senescent rats. In: Stein, D. (Ed.), Psychobiology of Aging: Problems and Perspectives. Elsevier, New York, pp. 253–272. Barnes, 1985, An age comparison of the rates of acquisition and forgetting of spatial information in relation to long-term enhancement of hippocampal synapses, Behav. Neurosci., 99, 1040, 10.1037/0735-7044.99.6.1040 Barnes, 1980, Spatial memory deficit in senescent rats, Can. J. Psychol., 34, 29, 10.1037/h0081022 Barnes, 1983, Loss of place specificity in hippocampal complex spike cells of senescent rat, Neurobiol. Aging, 4, 113, 10.1016/0197-4580(83)90034-9 Barnes, 1987, Behavioral and neurophysiological examples of functional sparing in senescent rat, Can. J. Psychol., 41, 131 Barnes, 1987, Increased electrotonic coupling in aged rat hippocampus: a possible mechanism for cellular excitability changes, J. Comp. Neurol., 259, 549, 10.1002/cne.902590405 Barnes, 1990, Acetyl-1-carnitine. 2. Effects on learning and memory performance of aged rats in simple and complex mazes, Neurobiol. Aging, 11, 499, 10.1016/0197-4580(90)90110-L Barnes, 1992, Region-specific age effects on AMPA sensitivity: electrophysiological evidence for loss of synaptic contacts in hippocampal field CA1, Hippocampus, 2, 457, 10.1002/hipo.450020413 Barnes, 1994, LTP saturation and spatial learning disruption: effects of task variables and saturation levels, J. Neurosci., 14, 5793, 10.1523/JNEUROSCI.14-10-05793.1994 Barnes, 1996, Functional integrity of NMDA-dependent LTP induction mechanisms across the lifespan of F344 rats, Learn. Mem., 3, 124, 10.1101/lm.3.2-3.124 Barnes, 1997, Age-related decrease in the N-methyl-d-aspartateR-mediated excitatory postsynaptic potential in hippocampal region CA1, Neurobiol. Aging, 18, 445, 10.1016/S0197-4580(97)00044-4 Barnes, 1997, Multistability of cognitive maps in the hippocampus of old rats, Nature, 388, 272, 10.1038/40859 Barnes, 2000, Chronic treatment of old rats with donepezil or galantamine: effects on memory, hippocampal plasticity and nicotinic receptors, Neuroscience, 99, 17, 10.1016/S0306-4522(00)00180-9 Barnes, 2000, LTP induction threshold change in old rats at the perforant path–granule cell synapse, Neurobiol. Aging, 21, 613, 10.1016/S0197-4580(00)00163-9 Barnes, 2000, Age-related decrease in the Schaffer collateral-evoked EPSP in awake, freely behaving rats, Neural Plast., 7, 167, 10.1155/NP.2000.167 Barria, 1997, Regulatory phosphorylation of AMPA-type glutamate receptors by CaMKII during long-term potentiation, Science, 276, 2042, 10.1126/science.276.5321.2042 Barrionuevo, 1980, The effects of repetitive low frequency stimulation on control and “potentiated” synaptic responses in the hippocampus, Life Sci., 27, 2385, 10.1016/0024-3205(80)90509-3 Bartus, 2000, On neurodegenerative diseases, models, and treatment strategies: lessons learned and lessons forgotten a generation following the cholinergic hypothesis, Exp. Neurol., 163, 495, 10.1006/exnr.2000.7397 Bartus, 1982, The cholinergic hypothesis of geriatric memory dysfunction, Science, 217, 408, 10.1126/science.7046051 Bashir, 1994, An investigation of depotentiation of long-term potentiation in the CA1 region of the hippocampus, Exp. Brain Res., 100, 437, 10.1007/BF02738403 Bauman, 1992, Age-dependence of effects of A1 adenosine receptor antagonism in rat hippocampal slices, J. Neurophysiol., 68, 629, 10.1152/jn.1992.68.2.629 Bear, 1996, Long-term depression in hippocampus, Annu. Rev. Neurosci., 19, 437, 10.1146/annurev.ne.19.030196.002253 Beatty, 1985, Preservation of accurate spatial memory in aged rats, Neurobiol. Aging, 6, 219, 10.1016/0197-4580(85)90053-3 Beatty, 1987, Effects of long-term restricted feeding on radial maze performance by aged rats, Neurobiol. Aging, 8, 325, 10.1016/0197-4580(87)90071-6 Benke, 1998, Modulation of AMPA receptor unitary conductance by synaptic activity, Nature, 393, 793, 10.1038/31709 Bergado, 1997, Chronic intraventricular infusion with NGF improves LTP in old cognitively-impaired rats, Brain Res., 770, 1, 10.1016/S0006-8993(97)00610-0 Bertoni-Freddari, 1986, Quantitative investigation of the morphological plasticity of synaptic junctions in rat dentate gyrus during aging, Brain Res., 366, 187, 10.1016/0006-8993(86)91294-1 Bienenstock, 1982, Theory for the development of neuron selectivity: orientation specificity and binocular interaction in visual cortex, J. Neurosci., 2, 23, 10.1523/JNEUROSCI.02-01-00032.1982 Bliss, 1993, A synaptic model of memory: long-term potentiation in the hippocampus, Nature, 361, 31, 10.1038/361031a0 Bliss, 1973, Long-lasting potentiation of synaptic transmission in the dentate area of the unanaesthetised rabbit following stimulation of the perforant path, J. Physiol. (London), 232, 357, 10.1113/jphysiol.1973.sp010274 Bliss, 1973, Long-lasting potentiation of synaptic transmission in the dentate area of the anesthetized rabbit following stimulus of perforant path, J. Physiol. (London), 232, 331, 10.1113/jphysiol.1973.sp010273 Blitzer, 1998, Gating of CaMKII by cAMP-regulated protein phosphatase activity during LTP, Science, 280, 1940, 10.1126/science.280.5371.1940 Blum, 1996, A model of spatial map formation in the hippocampus of the rat, Neural Comput., 8, 85, 10.1162/neco.1996.8.1.85 Bolhuis, 1992, Effects of intraventricular infusion of the N-methyl-d-aspartate (NMDA) receptor antagonist AP5 on spatial memory of rats in a radial arm maze, Behav. Brain Res., 47, 151, 10.1016/S0166-4328(05)80121-4 Bolshakov, 1994, Postsynaptic induction and presynaptic expression of hippocampal long-term depression, Science, 264, 1148, 10.1126/science.7909958 Borroni, 2000, Role of voltage-dependent calcium channel long-term potentiation (LTP) and NMDA LTP in spatial memory, J. Neurosci., 20, 9272, 10.1523/JNEUROSCI.20-24-09272.2000 Bortolotto, 2000, A role for protein kinase C in a form of metaplasticity that regulates the induction of long-term potentiation at CA1 synapses of the adult rat hippocampus, Eur. J. Neurosci., 12, 4055, 10.1046/j.1460-9568.2000.00291.x Bortolotto, 1994, A molecular switch activated by metabotropic glutamate receptors regulates induction of long-term potentiation, Nature, 368, 740, 10.1038/368740a0 Bortolotto, 1999, Roles of metabotropic glutamate receptors in LTP and LTD in the hippocampus, Curr. Opin. Neurobiol., 9, 299, 10.1016/S0959-4388(99)80044-0 Bourtchuladze, 1994, Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein, Cell, 79, 59, 10.1016/0092-8674(94)90400-6 Bramham, 1991, Activation of AP5-sensitive NMDA receptors is not required to induce LTP of synaptic transmission in the lateral perforant path, Eur. J. Neurosci., 3, 1300, 10.1111/j.1460-9568.1991.tb00062.x Bramham, 1991, Delta opioid receptor activation is required to induce LTP of synaptic transmission in the lateral perforant path in vivo, Brain Res., 567, 42, 10.1016/0006-8993(91)91433-2 Breindl, 1994, Opioid receptor-dependent long-term potentiation at the lateral perforant path–CA3 synapse in rat hippocampus, Brain Res. Bull., 33, 17, 10.1016/0361-9230(94)90045-0 Bruce, 1983, Spatial knowledge of young and elderly adults: scene recognition from familiar and novel perspectives, Exp. Aging Res., 9, 173, 10.1080/03610738308258447 Bures, 1997, Place cells and place navigation, Proc. Natl. Acad. Sci. U.S.A., 94, 343, 10.1073/pnas.94.1.343 Burwell, 1993, A longitudinal study of reaction time performance in Long–Evans rats, Neurobiol. Aging, 14, 57, 10.1016/0197-4580(93)90023-5 Cain, 1997, LTP, NMDA, genes and learning, Curr. Opin. Neurobiol., 7, 235, 10.1016/S0959-4388(97)80012-8 Calhoun, 1998, Hippocampal neuron and synaptophysin-positive bouton number in aging C57BL/6 mice, Neurobiol. Aging, 19, 599, 10.1016/S0197-4580(98)00098-0 Campbell, 1996, Aging changes in voltage-gated calcium currents in hippocampal CA1 neurons, J. Neurosci., 16, 6286, 10.1523/JNEUROSCI.16-19-06286.1996 Caplan, 1995, Age and gender differences in the effectiveness of map-like learning aids in memory for routes, J. Gerontol., 50, 126, 10.1093/geronb/50B.3.P126 Caprioli, 1991, Spatial learning and memory in the radial maze: a longitudinal study in rats from 4 to 25 months of age, Neurobiol. Aging, 12, 605, 10.1016/0197-4580(91)90093-Y Carroll, 1999, Rapid redistribution of glutamate receptors contributes to long-term depression in hippocampal cultures, Nat. Neurosci., 2, 454, 10.1038/8123 Castro, 1989, Recovery of spatial learning deficits after decay of electrically induced syanptic enhancement in the hippocampus, Nature, 342, 545, 10.1038/342545a0 Cave, 1991, Equivalent impairment of spatial and nonspatial memory following damage to the human hippocampus, Hippocampus, 1, 329, 10.1002/hipo.450010323 Cavus, 1996, Two forms of long-term potentiation in area CA1 activate different signal transduction cascades, J. Neurophysiol., 76, 3038, 10.1152/jn.1996.76.5.3038 Chang, 1991, Synapse formation occurs in association with the induction of long-term potentiation in two-year-old rat hippocampus in vitro, Neurobiol. Aging, 12, 517, 10.1016/0197-4580(91)90082-U Cherry, 1989, Age-related differences in three-dimensional spatial memory, J. Gerontol., 44, 16, 10.1093/geronj/44.1.P16 Cho, 2001, An experimental test of the role of postsynaptic calcium levels in determining synaptic strength using perirhinal cortex of rat, J. Physiol., 532, 459, 10.1111/j.1469-7793.2001.0459f.x Christie, 1997, Contribution of voltage-gated Ca2+ channels to homosynaptic long-term depression in the CA1 region in vitro, J. Neurophysiol., 77, 1651, 10.1152/jn.1997.77.3.1651 Clark, 1992, In vitro autoradiography of hippocampal excitatory amino acid binding in aged Fischer 344 rats: relationship to performance on the Morris water maze, Behav. Neurosci., 106, 324, 10.1037/0735-7044.106.2.324 Cohen, 1998, Priming of long-term potentiation induced by activation of metabotropic glutamate receptors coupled to phospholipase C, Hippocampus, 8, 160, 10.1002/(SICI)1098-1063(1998)8:2<160::AID-HIPO8>3.0.CO;2-P Coleman, 1987, Neuron numbers and dendritic extent in normal aging and Alzheimer’s disease, Neurobiol. Aging, 8, 521, 10.1016/0197-4580(87)90127-8 Collingridge, 1983, Excitatory amino acids in synaptic transmission in the Schaffer collateral–commissural pathway of the rat hippocampus, J. Physiol. (London), 334, 33, 10.1113/jphysiol.1983.sp014478 Collingridge, 1983, The antagonism of amino acid-induced excitation of rat hippocampal CA1 neurones in vitro, J. Physiol. (London), 334, 19, 10.1113/jphysiol.1983.sp014477 Colombo, 2002, Individual differences in spatial memory among aged rats are related to hippocampal PKCγ immunoreactivity, Hippocampus, 12, 285, 10.1002/hipo.10016 Colombo, 1997, Spatial memory is related to hippocampal subcellular concentrations of calcium-dependent protein kinase C isoforms in young and aged rats, Proc. Natl. Acad. Sci. U.S.A., 94, 14195, 10.1073/pnas.94.25.14195 Cooper, 2001, Temporary inactivation of the retrosplenial cortex causes a transient reorganization of spatial coding in the hippocampus, J. Neurosci., 21, 3986, 10.1523/JNEUROSCI.21-11-03986.2001 Corkin, 1984, Lasting consequences of bilateral medial temporal lobectomy: clinical course and experimental findings in H.M, Semin. Neurol., 4, 249, 10.1055/s-2008-1041556 Corkin, 2002, What’s new with the amnesic patient H.M.?, Nat. Rev. Neurosci., 3, 153, 10.1038/nrn726 Corkin, 1997, H.M.’s medial temporal lobe lesion: findings from magnetic resonance imaging, J. Neurosci., 17, 3964, 10.1523/JNEUROSCI.17-10-03964.1997 Coussens, 1996, Long-term potentiation induces synaptic plasticity at nontetanized adjacent synapses, Learn. Mem., 3, 106, 10.1101/lm.3.2-3.106 Coussens, 1996, Protein kinase and phosphatase activity regulate the form of synaptic plasticity expressed, Synapse, 24, 97, 10.1002/(SICI)1098-2396(199610)24:2<97::AID-SYN1>3.0.CO;2-9 Crook, 1986, Age-associated memory impairment: proposed diagnostic criteria and measures of clinical change. Report of a National Institute of Mental Health Work Group, Dev. Neuropsychol., 2, 261, 10.1080/87565648609540348 Cummings, 1996, Ca2+ signaling requirements for long-term depression in the hippocampus, Neuron, 16, 825, 10.1016/S0896-6273(00)80102-6 Danysz, 1988, Learning impairment in rats by N-methyl-d-aspartate receptor antagonists, Neuropharmacology, 27, 653, 10.1016/0028-3908(88)90189-X Davis, 1983, Improvement of 8-arm maze performance in aged Fischer 344 rats with 3,4-diaminopyridine, Exp. Aging Res., 9, 211, 10.1080/03610738308258454 Dayan, 1991, Optimising synaptic learning rules in linear associative memories, Biol. Cybern., 65, 253, 10.1007/BF00206223 Derkach, 1999, Ca2+/calmodulin-kinase II enhances channel conductance of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate type glutamate receptors, Proc. Natl. Acad. Sci. U.S.A., 96, 3269, 10.1073/pnas.96.6.3269 Derrick, 1994, Opioid receptor activation is one factor underlying the frequency dependence of mossy fiber LTP induction, J. Neurosci., 14, 4359, 10.1523/JNEUROSCI.14-07-04359.1994 Derrick, 1994, Frequency-dependent associative long-term potentiation at the hippocampal mossy fiber–CA3 synapse, Proc. Natl. Acad. Sci. U.S.A., 91, 10290, 10.1073/pnas.91.22.10290 Derrick, 1996, Associative, bidirectional modifications at the hippocampal mossy fibre–CA3 synapse, Nature, 381, 429, 10.1038/381429a0 Derrick, 1991, Opioid receptors are involved in an NMDA receptor-independent mechanism of LTP induction at hippocampal mossy fiber–CA3 synapses, Brain Res. Bull., 27, 219, 10.1016/0361-9230(91)90071-Q Derrick, 1992, Mu opioid receptors are associated with the induction of hippocampal mossy fiber long-term potentiation, J. Pharmacol. Exp. Ther., 263, 725 de Toledo-Morrell, 1985, Electrophysiological markers of aging and memory loss in rats, Ann. N. Y. Acad. Sci., 444, 296, 10.1111/j.1749-6632.1985.tb37598.x de Toledo-Morrell, 1984, Age dependent deficits in spatial memory are related to impaired hippocampal kindling, Behav. Neurosci., 98, 902, 10.1037/0735-7044.98.5.902 de Toledo-Morrell, 1984, Pentoxifylline reverses age related deficits in spatial memory, Behav. Neural Biol., 42, 1, 10.1016/S0163-1047(84)90364-9 de Toledo-Morrell, 1995, Gender differences in the vulnerability of the hippocampal formation during aging, Soc. Neurosci. Abstr., 21, 1708 Deupree, 1991, Spatial performance correlates with in vitro potentiation in young and aged Fischer 344 rats, Brain Res., 554, 1, 10.1016/0006-8993(91)90164-Q Deupree, 1993, Age-related alterations in potentiation in the CA1 region in F344 rats, Neurobiol. Aging, 14, 249, 10.1016/0197-4580(93)90009-Z Deyo, 1989, Nimodipine facilitates associative learning in aging rabbits, Science, 243, 809, 10.1126/science.2916127 Diana, 1994, Age and strain differences in rat place learning and hippocampal dentate gyrus frequency-potentiation, Neurosci. Lett., 171, 113, 10.1016/0304-3940(94)90618-1 Diana, 1994, Selective reduction of hippocampal dentate frequency potentiation in aged rats with impaired place learning, Brain Res. Bull., 35, 107, 10.1016/0361-9230(94)90089-2 Disterhoft, 1993, Functional aspects of calcium-channel modulation, Clin. Neuropharmacol., 16, S12, 10.1097/00002826-199316001-00003 Douglas, 1975, Long-term potentiation of the perforant path–granule cell synapse in the rat hippocampus, Brain Res., 86, 205, 10.1016/0006-8993(75)90697-6 Doyère, 1996, Low-frequency trains of paired stimuli induce long-term depression in area CA1 but not in dentate gyrus of the intact rat, Hippocampus, 6, 52, 10.1002/(SICI)1098-1063(1996)6:1<52::AID-HIPO9>3.0.CO;2-9 Dudek, 1992, Homosynaptic long-term depression in area CA1 of hippocampus and effects of N-methyl-d-aspartate receptor blockade, Proc. Natl. Acad. Sci. U.S.A., 89, 4363, 10.1073/pnas.89.10.4363 Dudek, 1993, Bidirectional long-term modification of synaptic effectiveness in the adult and immature hippocampus, J. Neurosci., 13, 2910, 10.1523/JNEUROSCI.13-07-02910.1993 Dunwiddie, 1978, Long-term potentiation and depression of synaptic responses in rat hippocampus: localization and frequency dependency, J. Physiol. (London), 276, 353, 10.1113/jphysiol.1978.sp012239 Eckles, 1997, Amelioration of age-related deficits in the stimulation of synapsin phosphorylation, Neurobiol. Aging, 18, 213, 10.1016/S0197-4580(97)00008-0 Eckles-Smith, 2000, Caloric restriction prevents age-related deficits in LTP and in NMDA receptor expression, Brain Res. Mol. Brain Res., 78, 154, 10.1016/S0169-328X(00)00088-7 Ekstrom, 2001, NMDA receptor antagonism blocks experience-dependent expansion of hippocampal “place fields”, Neuron, 31, 631, 10.1016/S0896-6273(01)00401-9 Enderlin, 1997, Aging decreases the abundance of retinoic acid (RAR) and triiodothyronine (TR) nuclear receptor mRNA in rat brain: effect of the administration of retinoids, FEBS Lett., 412, 629, 10.1016/S0014-5793(97)00845-4 Enderlin, 1997, Age-related decreases in mRNA for brain nuclear receptors and target genes are reversed by retinoic acid treatment, Neurosci. Lett., 229, 125, 10.1016/S0304-3940(97)00424-2 Erickson, 1993, Comparison of long-term enhancement and short-term exploratory modulation of perforant path synaptic transmission, Brain Res., 615, 275, 10.1016/0006-8993(93)90038-O Etchamendy, 2001, Alleviation of a selective age-related relational memory deficit in mice by pharmacologically induced normalization of brain retinoid signaling, J. Neurosci., 21, 6423, 10.1523/JNEUROSCI.21-16-06423.2001 Etienne, 1992, Navigation of a small mammal by dead reckoning and local cues, Curr. Dir. Psychol. Sci., 1, 48, 10.1111/1467-8721.ep11509737 Evans, 1984, Cognitive mapping and elderly adults: verbal and location memory for urban landmarks, J. Gerontol., 38, 452, 10.1093/geronj/39.4.452 Fanselow, 1994, Acquisition of contextual Pavlovian fear conditioning is blocked by application of an NMDA receptor antagonist d,l-2-amino-5-phosphonovaleric acid to the basolateral amygdala, Behav. Neurosci., 108, 210, 10.1037/0735-7044.108.1.210 Fanselow, 1994, Differential effects of the N-methyl-d-aspartate antagonist d,l-2-amino-5-phosphonovalerate on acquisition of fear of auditory and contextual cues, Behav. Neurosci., 108, 235, 10.1037/0735-7044.108.2.235 Fischer, 1987, Amelioration of cholinergic neuron atrophy and spatial memory impairment in aged rats by nerve growth factor, Nature, 329, 65, 10.1038/329065a0 Fischer, 1991, Progressive decline in spatial learning and integrity of forebrain cholinergic neurons in rats during aging, Neurobiol. Aging, 13, 9, 10.1016/0197-4580(92)90003-G Flicker, 1984, Effects of aging and dementia upon recent visuospatial memory, Neurobiol. Aging, 5, 275, 10.1016/0197-4580(84)90003-4 Foster, 1999, Involvement of hippocampal synaptic plasticity in age-related memory decline, Brain Res. Brain Res. Rev., 30, 236, 10.1016/S0165-0173(99)00017-X Foster, 2001, Mechanism for increased hippocampal synaptic strength following differential experience, J. Neurophysiol., 85, 1377, 10.1152/jn.2001.85.4.1377 Foster, 1997, Age-associated changes in Ca2+-dependent processes: relation to hippocampal synaptic plasticity, Hippocampus, 7, 602, 10.1002/(SICI)1098-1063(1997)7:6<602::AID-HIPO3>3.0.CO;2-G Foster, 1991, Increase in perforant path quantal size in aged F-344 rats, Neurobiol. Aging, 12, 441, 10.1016/0197-4580(91)90071-Q Foster, 1996, Mechanism of altered synaptic strength due to experience: relation to long-term potentiation, Brain Res., 736, 243, 10.1016/0006-8993(96)00707-X Foster, 2000, Receptor blockade reveals a correspondence between hippocampal-dependent behavior and experience-dependent synaptic enhancement, Brain Res., 871, 39, 10.1016/S0006-8993(00)02379-9 Foster, 2001, Calcineurin links Ca2+ dysregulation with brain aging, J. Neurosci., 21, 4066, 10.1523/JNEUROSCI.21-11-04066.2001 Fox, 1995, Polysialylated neural cell adhesion molecule expression by neurons and astroglial processes in the rat dentate gyrus declines dramatically with increasing age, Int. J. Dev. Neurosci., 13, 663, 10.1016/0736-5748(95)00067-4 Frenguelli, 1991, Electrogenic uptake contributes a major component of the depolarizing action of l-glutamate in rat hippocampal slices, Br. J. Pharmacol., 102, 355, 10.1111/j.1476-5381.1991.tb12178.x Frey, 1993, Effects of cAMP simulate a late stage of LTP in hippocampal CA1 neurons, Science, 260, 1661, 10.1126/science.8389057 Frick, 1995, Age-related spatial reference and working memory deficits assessed in the water maze, Neurobiol. Aging, 16, 149, 10.1016/0197-4580(94)00155-3 Fujii, 1991, Reversal of long-term potentiation (depotentiation) induced by tetanus stimulation of the input to CA1 neurons of guinea pig hippocampal slices, Brain Res., 555, 112, 10.1016/0006-8993(91)90867-U Gadian, 2000, Developmental amnesia associated with early hypoxic-ischaemic injury, Brain, 123, 499, 10.1093/brain/123.3.499 Gage, 1984, Intrahippocampal septal grafts ameliorate learning impairments in aged rats, Science, 225, 533, 10.1126/science.6539949 Gage, 1984, Spatial learning and motor deficits in aged rats, Neurobiol. Aging, 5, 43, 10.1016/0197-4580(84)90084-8 Gage, 1984, Regional changes in brain glucose metabolism reflect cognitive impairments in aged rats, J. Neurosci., 4, 2856, 10.1523/JNEUROSCI.04-11-02856.1984 Gage, 1989, Age-related impairments in spatial memory are independent of those in sensorimotor skills, Neurobiol. Aging, 10, 347, 10.1016/0197-4580(89)90047-X Gallagher, 1995, Aging: the cholinergic hypothesis of cognitive decline, Curr. Opin. Neurobiol., 5, 161, 10.1016/0959-4388(95)80022-0 Gallagher, 1988, Spatial learning deficits in old rats: a model for memory decline in the aged, Neurobiol. Aging, 9, 363, 10.1016/S0197-4580(88)80082-4 Gallagher, 1985, Effects of opiate antagonists on spatial memory in young and aged rats, Behav. Neural Biol., 44, 374, 10.1016/S0163-1047(85)90688-0 Gallagher, 1990, Markers for biogenic amines in the aged rat brain: relationship to decline in spatial learning ability, Neurobiol. Aging, 11, 507, 10.1016/0197-4580(90)90111-C Geinisman, 1979, Loss of axosomatic synapses in the dentate gyrus of aged rats, Brain Res., 168, 485, 10.1016/0006-8993(79)90304-4 Geinisman, 1999, Age-related decline in memory function: is it associated with a loss of synapses?, Neurobiol. Aging, 20, 353 Geinisman, 1976, Decrease in the number of synapses in the senescent brain: a quantitative electron microscopic analysis of the dentate gyrus molecular layer in the rat, Mech. Aging Dev., 5, 11, 10.1016/0047-6374(76)90003-8 Geinisman, 1977, Partial deafferentation of neurons in the dentate gyrus of the senescent rat, Brain Res., 134, 541, 10.1016/0006-8993(77)90828-9 Geinisman, 1986, Aged rats need a preserved complement of perforated axospinous synapses per hippocampal neuron to maintain good spatial memory, Brain Res., 398, 266, 10.1016/0006-8993(86)91486-1 Geinisman, 1986, Loss of perforated synapses in the dentate gyrus: morphological substrate of memory deficit in aged rats, Proc. Natl. Acad. Sci. U.S.A., 83, 3027, 10.1073/pnas.83.9.3027 Geinisman, 1992, Age-related loss of axospinous synapses formed by two afferent systems in the rat dentate gyrus as revealed by the unbiased stereological dissector technique, Hippocampus, 2, 437, 10.1002/hipo.450020411 Geinisman, 1995, Hippocampal markers of age-related memory dysfunction: behavioral, electrophysiological and morphological perspectives, Prog. Neurobiol., 45, 223, 10.1016/0301-0082(94)00047-L Giese, 1998, Autophosphorylation at Thr286 of the α calcium-calmodulin kinase II in LTP and learning, Science, 279, 870, 10.1126/science.279.5352.870 Godefroy, 1989, Age-related changes in dopaminergic and serotonergic indices in the rat forebrain, Neurobiol. Aging, 10, 187, 10.1016/0197-4580(89)90029-8 Gothard, 1996, Dynamics of mismatch correction in the hippocampal ensemble code for space: interaction between path integration and environmental cues, J. Neurosci., 16, 8027, 10.1523/JNEUROSCI.16-24-08027.1996 Gothard, 2001, Dentate gyrus and CA1 ensemble activity during spatial reference frame shifts in the presence and absence of visual input, J. Neurosci., 21, 7284, 10.1523/JNEUROSCI.21-18-07284.2001 Gould, 1999, Learning enhances adult neurogenesis in the hippocampal formation, Nat. Neurosci., 2, 260, 10.1038/6365 Granger, 1996, Facilitation of glutamate receptors reverses an age-associated memory impairment in rats, Synapse, 22, 332, 10.1002/(SICI)1098-2396(199604)22:4<332::AID-SYN4>3.0.CO;2-C Green, 1986, Altered synaptic transmission in dentate gyrus of rats reared in complex environments: evidence from hippocampal slices maintained in vitro, J. Neurophysiol., 55, 739, 10.1152/jn.1986.55.4.739 Green, 1990, Exploration-dependent modulation of evoked responses in fascia dentata: dissociation of motor, EEG, and sensory factors and evidence for a synaptic efficacy change, J. Neurosci., 10, 1455, 10.1523/JNEUROSCI.10-05-01455.1990 Grover, 1998, Evidence for postsynaptic induction and expression of NMDA receptor independent LTP, J. Neurophysiol., 79, 1167, 10.1152/jn.1998.79.3.1167 Grover, 1990, Two components of long-term potentiation induced by different patterns of afferent activation, Nature, 347, 477, 10.1038/347477a0 Grover, 1992, N-Methyl-d-aspartate receptor-independent long-term potentiation in area CA1 of rat hippocampus: input-specific induction and preclusion in a non-tetanized pathway, Neuroscience, 49, 7, 10.1016/0306-4522(92)90072-A Grover, 1994, Activation of NMDA receptors in hippocampal area CA1 by low and high frequency orthodromic stimulation and their contribution to induction of long-term potentiation, Synapse, 16, 66, 10.1002/syn.890160108 Gustafsson, 1988, Physiological mechanisms underlying long-term potentiation, Trends Neurosci., 11, 156, 10.1016/0166-2236(88)90142-7 Gustafsson, 1987, Long-term potentiation in the hippocampus using depolarizing current pulses as the conditioning stimulus to single volley synaptic potentials, J. Neurosci., 7, 774, 10.1523/JNEUROSCI.07-03-00774.1987 Haigler, 1985, Acetylcholine, aging and anatomy: differential effects in the hippocampus, Brain Res., 362, 157, 10.1016/0006-8993(86)91409-5 Hansel, 1997, Relation between dendritic Ca2+ levels and the polarity of synaptic long-term modifications in rat visual cortex neurons, Eur. J. Neurosci., 9, 2309, 10.1111/j.1460-9568.1997.tb01648.x Hasan, 1973, Ultrastructural age changes in hippocampal neurons, synapses and neuroglia, Exp. Gerontol., 8, 75, 10.1016/0531-5565(73)90017-X Hasselmo, 1999, Neuromodulation and the hippocampus: memory function and dysfunction in a network simulation, Prog. Brain Res., 121, 3, 10.1016/S0079-6123(08)63064-2 Hasselmo, 1999, Neuromodulation: acetylcholine and memory consolidation, Trends Cogn. Sci., 3, 351, 10.1016/S1364-6613(99)01365-0 Hasselmo, 1996, Encoding and retrieval of episodic memories: role of cholinergic and GABAergic modulation in the hippocampus, Hippocampus, 6, 693, 10.1002/(SICI)1098-1063(1996)6:6<693::AID-HIPO12>3.0.CO;2-W Hayashi, 1997, Somatostatin and brain-derived neurotrophic factor mRNA expression in the primate brain: decreased levels of mRNAs during aging, Brain Res., 749, 283, 10.1016/S0006-8993(96)01317-0 Hayashi, 2000, Driving AMPA receptors into synapses by LTP and CaMKII: requirement for GluR1 and PDZ domain interaction, Science, 287, 2262, 10.1126/science.287.5461.2262 Hayashi, 2001, Changes in BDNF-immunoreactive structures in the hippocampal formation of the aged macaque monkey, Brain Res., 918, 191, 10.1016/S0006-8993(01)03002-5 Hebb, D.O., 1949. The Organization of Behavior. Wiley, New York. Henriksson, 1992, Hippocampal nerve growth factor levels are related to spatial learning ability in aged rats, Behav. Brain Res., 48, 15, 10.1016/S0166-4328(05)80134-2 Hersi, 1995, Dopamine D1 receptor ligands modulate cognitive performance and hippocampal acetylcholine release in memory-impaired aged rats, Neuroscience, 69, 1067, 10.1016/0306-4522(95)00319-E Heynen, 1996, Bidirectional modification of CA1 synapses in the adult hippocampus in vivo, Nature, 381, 163, 10.1038/381163a0 Heynen, 2000, Bidirectional, activity-dependent regulation of glutamate receptors in the adult hippocampus in vivo, Neuron, 28, 527, 10.1016/S0896-6273(00)00130-6 Hill, 1978, First occurrence of hippocampal spatial firing in a new environment, Exp. Neurol., 62, 282, 10.1016/0014-4886(78)90058-4 Hill, 1981, Effects of deafness and blindness on the spatial correlates of hippocampal unit activity in the rat, Exp. Neurol., 74, 204, 10.1016/0014-4886(81)90159-X Hinton, G.E., Anderson, J.A., 1981. Parallel Models of Associative Memory. Lawrence Erlbaum Associates, Hillsdale. Hirsh, 1974, The hippocampus and contextual retrieval of information from memory: a theory, Behav. Biol., 12, 421, 10.1016/S0091-6773(74)92231-7 Hoff, 1982, Lesion-induced synaptogenesis in the dentate gyrus of aged rats. I. Loss and reacquisition of normal synaptic density, J. Comp. Neurol., 205, 246, 10.1002/cne.902050304 Holland, 1998, Primed facilitation of homosynaptic long-term depression and depotentiation in rat hippocampus, J. Neurosci., 18, 887, 10.1523/JNEUROSCI.18-03-00887.1998 Hollingsworth, 1985, Biochemical characterization of a filtered synaptoneurosome preparation from guinea pig cerebral cortex: cyclic adenosine 3′:5′-monophosphate-generating systems, receptors, and enzymes, J. Neurosci., 5, 2240, 10.1523/JNEUROSCI.05-08-02240.1985 Hopfield, 1982, Neural networks and physical systems with emergent collective computational abilities, Proc. Natl. Acad. Sci. U.S.A., 79, 2554, 10.1073/pnas.79.8.2554 Huang, 1995, D1/D5 receptor agonists induce a protein synthesis-dependent late potentiation in the CA1 region of the hippocampus, Proc. Natl. Acad. Sci. U.S.A., 92, 2446, 10.1073/pnas.92.7.2446 Huerta, 1993, Heightened synaptic plasticity of hippocampal CA1 neurons during a cholinergically induced rhythmic state, Nature, 364, 723, 10.1038/364723a0 Idrobo, 1987, Dietary restriction: effects on radial maze learning and lipofuscin pigment deposition in the hippocampus and frontal cortex, Arch. Gerontol. Geriatr., 6, 355, 10.1016/0167-4943(87)90014-8 Ikonen, 2002, Cholinergic system regulation of spatial representation by the hippocampus, Hippocampus, 12, 386, 10.1002/hipo.1109 Ingram, 1985, Analysis of age-related impairments in learning and memory in rodent models, Ann. N. Y. Acad. Sci., 444, 312, 10.1111/j.1749-6632.1985.tb37599.x Ingram, 1994, Chronic nimodipine treatment in aged rats: analysis of motor and cognitive effects and muscarinic-induced striatal dopamine release, Neurobiol. Aging, 15, 55, 10.1016/0197-4580(94)90144-9 Isaac, 1995, Evidence for silent synapses: implications for the expression of LTP, Neuron, 15, 427, 10.1016/0896-6273(95)90046-2 Ishihara, 1990, Different drug-susceptibilities of long-term potentiation in three input systems to the CA3 region of the guinea pig hippocampus in vitro, Neuropharmacology, 29, 487, 10.1016/0028-3908(90)90171-M Jarrard, 1993, On the role of the hippocampus in learning and memory in the rat, Behav. Neural Biol., 60, 9, 10.1016/0163-1047(93)90664-4 Jeffery, 1999, Learned interaction of visual and idiothetic cues in the control of place field orientation, Exp. Brain Res., 127, 151, 10.1007/s002210050785 Johnston, 1992, NMDA-receptor-independent long-term potentiation, Annu. Rev. Physiol., 54, 489, 10.1146/annurev.ph.54.030192.002421 Kameyama, 1998, Involvement of a postsynaptic protein kinase A substrate in the expression of homosynaptic long-term depression, Neuron, 21, 1163, 10.1016/S0896-6273(00)80633-9 Kampen, 1994, Estrogen use and verbal memory in healthy postmenopausal women, Obstet. Gynecol., 83, 979, 10.1097/00006250-199406000-00017 Kelly, 2000, Deficits in nerve growth factor release and tyrosine receptor kinase phosphorylation are associated with age-related impairment in long-term potentiation in the dentate gyrus, Neuroscience, 95, 359, 10.1016/S0306-4522(99)00460-1 Kemp, 1997, NMDA receptor-dependent and -independent long-term depression in the CA1 region of the adult rat hippocampus in vitro, Neuropharmacology, 36, 397, 10.1016/S0028-3908(96)90015-5 Kemp, 2001, Long-term depression: a cascade of induction and expression mechanisms, Prog. Neurobiol., 65, 339, 10.1016/S0301-0082(01)00013-2 Kemp, 2000, Different forms of LTD in the CA1 region of the hippocampus: role of age and stimulus protocol, Eur. J. Neurosci., 12, 360, 10.1046/j.1460-9568.2000.00903.x Kempermann, 1999, Experience-dependent regulation of adult hippocampal neurogenesis: effects of long-term stimulation and stimulus withdrawal, Hippocampus, 9, 321, 10.1002/(SICI)1098-1063(1999)9:3<321::AID-HIPO11>3.0.CO;2-C Kempermann, 1997, More hippocampal neurons in adult mice living in an enriched environment, Nature, 386, 493, 10.1038/386493a0 Kempermann, 1998, Experience-induced neurogenesis in the senescent dentate gyrus, J. Neurosci., 18, 3206, 10.1523/JNEUROSCI.18-09-03206.1998 Kentros, 1998, Abolition of long-term stability of new hippocampal place cell maps by NMDA receptor blockade, Science, 280, 2121, 10.1126/science.280.5372.2121 Kerr, 1989, Corticosteroid modulation of hippocampal potentials: increased effect with aging, Science, 245, 1505, 10.1126/science.2781293 Kerr, 1991, Chronic stress-induced acceleration of electrophysiologic and morphometric biomarkers of hippocampal aging, J. Neurosci., 11, 1316, 10.1523/JNEUROSCI.11-05-01316.1991 Khachaturian, Z.S., 1984. Towards theories of brain aging. In: Kay, D., Burrows, G.D. (Eds.), Handbook of Studies on Psychiatry and Old Age. Elsevier, Amsterdam, pp. 7–30. Kirasic, 1991, Spatial cognition and behavior in young and elderly adults: implication for learning new environments, Psychol. Aging, 6, 10, 10.1037/0882-7974.6.1.10 Kirasic, K.C., Allen, G.C., 1985. Aging, spatial performance and competence. In: Charness, N. (Ed.), Aging and Human Performance. Wiley, New York, pp. 191–224. Kirasic, 1990, Acquisition of spatial knowledge under conditions of temporospatial discontinuity in young and elderly adults, Psychol. Res., 52, 76, 10.1007/BF00867215 Kirasic, 1992, Age-related differences in adults’ macrospatial cognitive processes, Exp. Aging Res., 18, 33, 10.1080/03610739208253908 Knierim, 1995, Place cells, head direction cells, and the learning of landmark stability, J. Neurosci., 15, 1648, 10.1523/JNEUROSCI.15-03-01648.1995 Kohonen, T., 1978. Associative Memory: A System-Theoretic Approach. Springer-Verlag, New York. Kral, 1977. Benign senescent forgetfulness. In: Katzman, R., Terry, R.D., Bick, K.L. (Eds.), Alzheimer’s Disease, Senile Dementia and Related Disorders, vol. 7. Raven Press, New York, pp. 47–51. Kubie, J.L., Ranck Jr., J.B., 1983. Sensory-behavioral correlates in individual hippocampus neurons in three situations: space and context. In: Seifert, W. (Ed.), Neurobiology of the Hippocampus. Academic Press, New York, pp. 433–447. Kullmann, 1995, The site of expression of NMDA receptor-dependent LTP: new fuel for an old fire, Neuron, 15, 997, 10.1016/0896-6273(95)90089-6 Landfield, P.W., 1980. Correlative studies of brain neurophysiology and behavior during aging. In: Stein, D. (Ed.), The Psychobiology of Aging: Problems and Perspectives. Elsevier, Amsterdam, pp. 227–251. Landfield, 1987, “Increased calcium current” hypothesis of brain aging, Neurobiol. Aging, 8, 346, 10.1016/0197-4580(87)90074-1 Landfield, 1988, Hippocampal neurobiological mechanisms of age-related memory dysfunction, Neurobiol. Aging, 9, 571, 10.1016/S0197-4580(88)80116-7 Landfield, 1977, Impaired monosynaptic potentiation in in vitro hippocampal slices from aged, memory-deficient rats, J. Gerontol., 32, 523, 10.1093/geronj/32.5.523 Landfield, 1984, Chronically elevating plasma Mg2+ improves hippocampal frequency potentiation and reversal learning in aged and young rats, Brain Res., 332, 167, 10.1016/0006-8993(84)91199-5 Landfield, 1984, Prolonged Ca2+-dependent after hyperpolarizations in hippocampal neurons of aged rats, Science, 226, 1089, 10.1126/science.6494926 Landfield, 1978, Impaired synaptic potentiation process in the hippocampus of aged, memory deficient rats, Brain Res., 150, 85, 10.1016/0006-8993(78)90655-8 Landfield, 1981, Brain-aging correlates: retardation by hormonal–pharmacological treatments, Science, 214, 581, 10.1126/science.6270791 Landfield, 1986, The effects of high Mg2+-to-Ca2+ ratios on frequency potentiation in hippocampal slices of young and aged rats, J. Neurophysiol., 56, 797, 10.1152/jn.1986.56.3.797 Larson, 1986, Patterned stimulation at the theta frequency is optimal for the induction of hippocampal long-term potentiation, Brain Res., 368, 347, 10.1016/0006-8993(86)90579-2 Lee, 1998, NMDA induces long-term synaptic depression and dephosphorylation of the GluR1 subunit of AMPA receptors in hippocampus, Neuron, 21, 1151, 10.1016/S0896-6273(00)80632-7 Lee, 2000, Regulation of distinct AMPA receptor phosphorylation sites during bidirectional synaptic plasticity, Nature, 405, 955, 10.1038/35016089 Lenck-Santini, 2001, Evidence for a relationship between place-cell spatial firing and spatial memory performance, Hippocampus, 11, 377, 10.1002/hipo.1052 Levere, 1992, Old age and cognition: enhancement of recent memory in aged rats by the calcium channel blocker nimodipine, Neurobiol. Aging, 13, 63, 10.1016/0197-4580(92)90010-U Levy, W.B., 1989. A Computational Approach to Hippocampal Function. Academic Press, New York. Levy, 1979, Synapses as associative memory elements in the hippocampal formation, Brain Res., 175, 233, 10.1016/0006-8993(79)91003-5 Li, 1997, NMDA but not AMPA receptor antagonists impair the delay-interposed radial maze performance of rats, Pharmacol. Biochem. Behav., 58, 249, 10.1016/S0091-3057(97)00015-4 Liao, 1995, Activation of postsynaptically silent synapses during LTP in CA1 region of hippocampal slice, Nature, 375, 400, 10.1038/375400a0 Light, 1983, Memory for spatial information in young and old adults, Dev. Psychol., 19, 901, 10.1037/0012-1649.19.6.901 Lindner, 1988, Aging and atropine effects on spatial navigation in the Morris water task, Behav. Neurosci., 102, 621, 10.1037/0735-7044.102.5.621 Lipman, 1992, Adult age differences in memory for routes: effects of instruction and spatial diagram, Psychol. Aging, 7, 435, 10.1037/0882-7974.7.3.435 Lippa, 1980, Brain cholinergic dysfunction and memory in aged rats, Neurobiol. Aging, 1, 13, 10.1016/0197-4580(80)90019-6 Lippa, 1981, Age-related alterations in neurotransmitter receptors: an electrophysiological and biochemical analysis, Neurobiol. Aging, 2, 3, 10.1016/0197-4580(81)90052-X Lisman, 1989, A mechanism for the Hebb and the anti-Hebb processes underlying learning and memory, Proc. Natl. Acad. Sci. U.S.A., 86, 9574, 10.1073/pnas.86.23.9574 Lisman, 2001, A model of synaptic memory: a CaMKII/PP1 switch that potentiates transmission by organizing an AMPA receptor anchoring assembly, Neuron, 31, 191, 10.1016/S0896-6273(01)00364-6 Lisman, 2002, The molecular basis of CaMKII function in synaptic and behavioural memory, Nat. Rev. Neurosci., 3, 175, 10.1038/nrn753 Lovinger, 1987, Protein kinase C stimulators produce a synapse specific increase in the endurance of long-term potentiation, Brain Res., 436, 177, 10.1016/0006-8993(87)91573-3 Luine, 1990, Spatial memory deficits in aged rats: contributions of monoaminergic systems, Brain Res., 537, 271, 10.1016/0006-8993(90)90368-L Luscher, 2001, Restless AMPA receptors: implications for synaptic transmission and plasticity, Trends Neurosci., 24, 665, 10.1016/S0166-2236(00)01959-7 Luscher, 2000, Synaptic plasticity and dynamic modulation of the postsynaptic membrane, Nat. Neurosci., 3, 545, 10.1038/75714 Lyford, 1993, Determinants of non-spatial working memory deficits in rats given intraventricular infusions of the NMDA antagonist AP5, Neuropsychologia, 31, 1079, 10.1016/0028-3932(93)90034-W Lynch, 1998, Age-related impairment in long-term potentiation in hippocampus: a role for the cytokine, interleukin-1β?, Prog. Neurobiol., 56, 571, 10.1016/S0301-0082(98)00054-9 Lynch, 1984, The biochemistry of memory: a new and specific hypothesis, Science, 224, 1057, 10.1126/science.6144182 Lynch, 1994, Membrane arachidonic acid concentration correlates with age and induction of long-term potentiation in the dentate gyrus of the rat, Eur. J. Neurosci., 6, 1008, 10.1111/j.1460-9568.1994.tb00595.x Lynch, 1977, Heterosynaptic depression: a post-synaptic correlate of long-term potentiation, Nature, 266, 737, 10.1038/266737a0 Lynch, 1983, Intracellular injections of EGTA block induction of hippocampal long-term potentiation, Nature, 305, 719, 10.1038/305719a0 Lynch, 1997, Evidence that a positive modulator of AMPA-type glutamate receptors improves delayed recall in aged humans, Exp. Neurol., 145, 89, 10.1006/exnr.1997.6447 Magee, J.C., 2002. Synaptic and non-synaptic mechanisms for plasticity and learning. In: Proceedings of the Winter Conference on Neural Plasticity. Moorea, French Polynesia. Magnusson, 1993, Effects of aging on NMDA and MK801 binding sites in mice, Brain Res., 604, 334, 10.1016/0006-8993(93)90386-2 Magnusson, 1993, Age-related changes in excitatory amino acid receptors in two mouse strains, Neurobiol. Aging, 14, 197, 10.1016/0197-4580(93)90001-R Maguire, 1996, Topographical disorientation following unilateral temporal lobe lesions in humans, Neuropsychologia, 34, 993, 10.1016/0028-3932(96)00022-X Malenka, 1999, Long-term potentiation—a decade of progress?, Science, 285, 1870, 10.1126/science.285.5435.1870 Malenka, 1989, An essential role for postsynaptic calmodulin and protein kinase activity in long-term potentiation, Nature, 340, 554, 10.1038/340554a0 Malinow, 2002, AMPA receptor trafficking and synaptic plasticity, Annu. Rev. Neurosci., 25, 103, 10.1146/annurev.neuro.25.112701.142758 Malinow, 1988, Persistent protein kinase activity underlying long-term potentiation, Nature, 335, 820, 10.1038/335820a0 Malinow, 1989, Inhibition of postsynaptic PKC or CaMKII blocks induction but not expression of LTP, Science, 245, 862, 10.1126/science.2549638 Malleret, 2001, Inducible and reversible enhancement of learning, memory, and long-term potentiation by genetic inhibition of calcineurin, Cell, 104, 675, 10.1016/S0092-8674(01)00264-1 Manahan-Vaughan, 1997, Group 1 and 2 metabotropic glutamate receptors play differential roles in hippocampal long-term depression and long-term potentiation in freely moving rats, J. Neurosci., 17, 3303, 10.1523/JNEUROSCI.17-09-03303.1997 Markowska, 1989, Individual differences in aging: behavioral and neurobiological correlates, Neurobiol. Aging, 10, 31, 10.1016/S0197-4580(89)80008-9 Markus, 1994, Spatial information content and reliability of hippocampal CA1 neurons: effects of visual input, Hippocampus, 4, 410, 10.1002/hipo.450040404 Markus, 1995, Interactions between location and task affect the spatial and directional firing of hippocampal neurons, J. Neurosci., 15, 7079, 10.1523/JNEUROSCI.15-11-07079.1995 Marr, 1971, Simple memory: a theory for archicortex, Philos.Trans. R. Soc. B: Biol. Sci., 262, 23, 10.1098/rstb.1971.0078 Martin, 1983, Naloxone and long term potentiation of hippocampal CA3 field potentials in vitro, Neuropeptides, 4, 45, 10.1016/0143-4179(83)90007-0 Martin, 2000, Synaptic plasticity and memory: an evaluation of the hypothesis, Annu. Rev. Neurosci., 23, 649, 10.1146/annurev.neuro.23.1.649 Mayford, 1996, Control of memory formation through regulated expression of a CaMKII transgene, Science, 274, 1678, 10.1126/science.274.5293.1678 McClelland, J.L., Rumelhart, D.E., 1986. Parallel Distributed Processing: Explorations in the Microstructure of Cognition. MIT Press, Cambridge. McGahon, 1997, The ability of aged rats to sustain long-term potentiation is restored when the age-related decrease in membrane arachidonic acid concentration is reversed, Neuroscience, 81, 9, 10.1016/S0306-4522(97)00116-4 McGahon, 1999, Activation of p42 mitogen-activated protein kinase by arachidonic acid and trans-1-amino-cyclopentyl-1,3-dicarboxylate impacts on long-term potentiation in the dentate gyrus in the rat: analysis of age-related changes, Neuroscience, 90, 1167, 10.1016/S0306-4522(98)00528-4 McGahon, 1999, Age-related changes in synaptic function: analysis of the effect of dietary supplementation with omega-3 fatty acids, Neuroscience, 94, 305, 10.1016/S0306-4522(99)00219-5 McGahon, 1999, Age-related changes in LTP and antioxidant defenses are reversed by an α-lipoic acid-enriched diet, Neurobiol. Aging, 20, 655, 10.1016/S0197-4580(99)00050-0 McGahon, 1999, Age-related changes in oxidative mechanisms and LTP are reversed by dietary manipulation, Neurobiol. Aging, 20, 643, 10.1016/S0197-4580(99)00027-5 McKernan, 1997, Fear conditioning induces a lasting potentiation of synaptic currents in vitro, Nature, 390, 607, 10.1038/37605 McMonagle-Strucko, 1993, Enhanced acquisition of reversal training in a spatial learning task in rats treated with chronic nimodipine, Pharmacol. Biochem. Behav., 44, 827, 10.1016/0091-3057(93)90013-J McNaughton, 1987, Hippocampal synaptic enhancement and information storage within a distributed memory system, Trends Neurosci., 10, 408, 10.1016/0166-2236(87)90011-7 McNaughton, 1978, Synaptic enhancement in fascia dentata: cooperativity among coactive afferents, Brain Res., 157, 277, 10.1016/0006-8993(78)90030-6 McNaughton, 1981, Synaptic efficacy and EPSP summation in granule cells of rat fascia dentata studied in vitro, J. Neurophysiol., 46, 952, 10.1152/jn.1981.46.5.952 McNaughton, 1983, The contributions of position, direction, and velocity to single unit activity in the hippocampus of freely-moving rats, Exp. Brain Res., 52, 41, 10.1007/BF00237147 McNaughton, 1986, Long-term enhancement of hippocampal synaptic transmission and the acquisition of spatial information, J. Neurosci., 6, 563, 10.1523/JNEUROSCI.06-02-00563.1986 McNaughton, 1989, Cortical–hippocampal interactions and cognitive mapping: a hypothesis based on reintegration of the parietal and inferotemporal pathways for visual processing, Psychobiology, 17, 230, 10.1007/BF03337774 McNaughton, 1996, Deciphering the hippocampal polyglot: the hippocampus as a path integration system, J. Exp. Biol., 199, 173, 10.1242/jeb.199.1.173 McWilliams, 1984, Synaptic density and axonal sprouting in rat hippocampus: stability in adulthood and decline in late adulthood, Brain Res., 294, 152, 10.1016/0006-8993(84)91321-0 Meaney, 1988, Effect of neonatal handling on age-related impairments associated with the hippocampus, Science, 239, 766, 10.1126/science.3340858 Mehta, 1997, Experience-dependent, asymmetric expansion of hippocampal place fields, Proc. Natl. Acad. Sci. U.S.A., 94, 8918, 10.1073/pnas.94.16.8918 Merrill, 2000, Conservation of neuron number and size in entorhinal cortex layers II, III and V/VI of aged primates, J. Comp. Neurol., 422, 396, 10.1002/1096-9861(20000703)422:3<396::AID-CNE6>3.0.CO;2-R Mishkin, M., Malamut, B.J., Bachevalier, J., 1984. Memories and habits: two neural systems. In: Lynch, G., McGaugh J.L., Weinberger, N.M. (Eds.), Neurobiology of Learning and Memory. Guilford Press, New York, pp. 65–88. Mittelstaedt, 1980, Homing by path integration in a mammal, Naturwissenschaften, 67, 566, 10.1007/BF00450672 Mizumori, 1994, Reversible inactivation of the lateral dorsal thalamus disrupts hippocampal place representation and impairs spatial learning, Brain Res., 644, 168, 10.1016/0006-8993(94)90361-1 Mizumori, 1996, Redistribution of spatial representation in the hippocampus of aged rats performing a spatial memory task, Behav. Neurosci., 110, 1006, 10.1037/0735-7044.110.5.1006 Moffat, 2001, Age differences in spatial memory in a virtual environment navigation task, Neurobiol. Aging, 22, 787, 10.1016/S0197-4580(01)00251-2 Moody, 1999, A nitric oxide-independent and beta-adrenergic receptor-sensitive form of metaplasticity limits theta-frequency stimulation-induced LTP in the hippocampal CA1 region, Learn. Mem., 6, 619, 10.1101/lm.6.6.619 Moore, 1993, Hippocampal plasticity induced by primed burst, but not long-term potentiation, stimulation is impaired in area CA1 of aged Fischer 344 rats, Hippocampus, 3, 57, 10.1002/hipo.450030106 Morgan, 1999, VDCCs and NMDARs underlie two forms of LTP in CA1 hippocampus in vivo, J. Neurophysiol., 82, 736, 10.1152/jn.1999.82.2.736 Morgan, 2001, Epileptic-like activity induces multiple forms of plasticity in hippocampal area CA1, Brain Res., 917, 90, 10.1016/S0006-8993(01)02913-4 Morgan, 2001, Electrical stimuli patterned after the theta-rhythm induce multiple forms of LTP, J. Neurophysiol., 86, 1289, 10.1152/jn.2001.86.3.1289 Morgan, 2001, Depotentiation of vdccLTP requires NMDAR activation, Neurobiol. Learn. Mem., 76, 229, 10.1006/nlme.2001.4016 Morris, 1981, Spatial localization does not require the presence of local cues, Learn. Motiv., 12, 239, 10.1016/0023-9690(81)90020-5 Morris, 1989, Synaptic plasticity and learning: selective impairment of learning in rats and blockade of long-term potentiation in vivo by the N-methyl-d-aspartate receptor antagonist AP5, J. Neurosci., 9, 3040, 10.1523/JNEUROSCI.09-09-03040.1989 Morris, 1986, Selective impairment of learning and blockade of long-term potentiation by an N-methyl-d-aspartate receptor antagonist, AP5, Nature, 319, 774, 10.1038/319774a0 Morris, 1990, Ibotenate lesions of hippocampus and/or subiculum: dissociating components of allocentric spatial learning, Eur. J. Neurosci., 2, 1016, 10.1111/j.1460-9568.1990.tb00014.x Moser, 1993, Association between brain temperature and dentate field potentials in exploration and swimming rats, Science, 259, 1324, 10.1126/science.8446900 Moser, 1993, Synaptic potentiation in the rat dentate gyrus during exploratory learning, NeuroReport, 5, 317, 10.1097/00001756-199312000-00035 Moser, 1998, Impaired spatial learning after saturation of long-term potentiation, Science, 281, 2038, 10.1126/science.281.5385.2038 Moyer, 1992, Nimodipine increases excitability of rabbit CA1 pyramidal neurons in an age- and concentration-dependent manner, J. Neurophysiol., 68, 2100, 10.1152/jn.1992.68.6.2100 Mulkey, 1992, Mechanisms underlying induction of homosynaptic long-term depression in the area CA1 of the hippocampus, Neuron, 9, 967, 10.1016/0896-6273(92)90248-C Mulkey, 1993, An essential role for protein phosphatases in hippocampal long-term depression, Science, 261, 1051, 10.1126/science.8394601 Mulkey, 1994, Involvement of a calcineurin/inhibitor-1 phosphatase cascade in hippocampal long-term depression, Nature, 369, 486, 10.1038/369486a0 Muller, 1996, A quarter of a century of place cells, Neuron, 17, 813, 10.1016/S0896-6273(00)80214-7 Muller, 1987, The effects of changes in the environment on the spatial firing of hippocampal complex-spike cells, J. Neurosci., 7, 1951, 10.1523/JNEUROSCI.07-07-01951.1987 Murray, 1998, Evidence that increased hippocampal expression of the cytokine interleukin-1β is a common trigger for age- and stress-induced impairments in long-term potentiation, J. Neurosci., 18, 2974, 10.1523/JNEUROSCI.18-08-02974.1998 Murray, 1998, Dietary supplementation with vitamin E reverses the age-related deficit in long term potentiation in dentate gyrus, J. Biol. Chem., 273, 12161, 10.1074/jbc.273.20.12161 Murray, 1998, Monkeys with rhinal cortex damage or neurotoxic hippocampal lesions are impaired on spatial scene learning and object reversals, Behav. Neurosci., 112, 1291, 10.1037/0735-7044.112.6.1291 Naveh-Benjamin, 1987, Coding of spatial location information: an automatic process?, J. Exp. Psychol. Learn. Mem. Cogn., 13, 595, 10.1037/0278-7393.13.4.595 Newman, 2000, Spatial memory and aging: performance on a human analog of the Morris water maze, Aging Neuropyschol. Cogn., 7, 86, 10.1076/1382-5585(200006)7:2;1-U;FT086 Nicolle, 1999, Metabotropic glutamate receptor-mediated hippocampal phosphoinositide turnover is blunted in spatial learning-impaired aged rats, J. Neurosci., 19, 9604, 10.1523/JNEUROSCI.19-21-09604.1999 Nicolle, 1999, No loss of synaptic proteins in the hippocampus of aged, behaviorally impaired rats, Neurobiol. Aging, 20, 343 Niesen, 1988, Reversed ethanol effects on potassium conductances in aged hippocampal dentate granule neurons, Brain Res., 445, 137, 10.1016/0006-8993(88)91082-7 Norris, 1996, Increased susceptibility to induction of long-term depression and long-term potentiation reversal during aging, J. Neurosci., 16, 5382, 10.1523/JNEUROSCI.16-17-05382.1996 Norris, 1998, Reversal of age-related alterations in synaptic plasticity by blockade of L-type Ca2+ channels, J. Neurosci., 18, 3171, 10.1523/JNEUROSCI.18-09-03171.1998 Norris, 1998, Alterations in the balance of protein kinase/phophatase activities parallel reduced synaptic strength during aging, J. Neurosphysiol., 80, 1567, 10.1152/jn.1998.80.3.1567 O’Dell, 1991, Long-term potentiation in the hippocampus is blocked by tyrosine kinase inhibitors, Nature, 353, 558, 10.1038/353558a0 O’Donnell, 2000, Age-related impairment in LTP is accompanied by enhanced activity of stress-activated protein kinases: analysis of underlying mechanisms, Eur. J. Neurosci., 12, 345, 10.1046/j.1460-9568.2000.00900.x Ohta, R.J., Kirasic, K.C., 1983. The investigation of environmental learning in the elderly. In: Rowles, G.D., Ohta, R.J. (Eds.), Aging and Milieu. Academic Press, New York, pp. 83–95. Ohta, 1981, Spatial perspective-taking in young and elderly adults, Exp. Aging Res., 7, 45, 10.1080/03610738108259785 O’Keefe, 1976, Place units in the hippocampus of the freely moving rat, Exp. Neurol., 51, 78, 10.1016/0014-4886(76)90055-8 O’Keefe, 1996, Geometric determinants of the place fields of hippocampal neurons, Nature, 381, 381 O’Keefe, 1978, Hippocampal place units in the freely moving rat: why they fire where they fire, Exp. Brain Res., 31, 573 O’Keefe, 1971, The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat, Brain Res., 34, 171, 10.1016/0006-8993(71)90358-1 O’Keefe, J., Nadel, L., 1978. The Hippocampus as a Cognitive Map. Clarendon Press, Oxford. O’Keefe, 1987, Single unit activity in the rat hippocampus during a spatial memory task, Exp. Brain Res., 68, 1 Oler, 1998, Age-related deficits on the radial maze and in fear conditioning: hippocampal processing and consolidation, Hippocampus, 8, 402, 10.1002/(SICI)1098-1063(1998)8:4<402::AID-HIPO8>3.0.CO;2-I Oler, 2000, Age-related deficits in the ability to encode contextual change: a place cell analysis, Hippocampus, 10, 338, 10.1002/1098-1063(2000)10:3<338::AID-HIPO14>3.0.CO;2-Y Olton, 1976, Remembrance of places passed: spatial memory in rats, J. Exp. Psychol. Anim. Behav. Process., 2, 97, 10.1037/0097-7403.2.2.97 O’Reilly, 1994, Hippocampal conjunctive encoding, storage, and recall: avoiding a trade-off, Hippocampus, 4, 661, 10.1002/hipo.450040605 Otani, 1995, Long-term depression of naive synapses in adult hippocampus induced by asynchronous synaptic activity, J. Neurophysiol., 73, 2596, 10.1152/jn.1995.73.6.2596 Otnaess, 1999, Pretraining prevents spatial learning impairment after saturation of hippocampal long-term potentiation, J. Neurosci., 19, 41 Ouanounou, 1999, Differential modulation of synaptic transmission by calcium chelators in young and aged hippocampal CA1 neurons: evidence for altered calcium homeostatsis in aging, J. Neurosci., 19, 906, 10.1523/JNEUROSCI.19-03-00906.1999 Packard, 1996, Inactivation of hippocampus or caudate nucleus with lidocaine differentially affects expression of place and response learning, Neurobiol. Learn. Mem., 65, 65, 10.1006/nlme.1996.0007 Packard, 1989, Differential effects of fornix and caudate nucleus lesions on two radial maze tasks: evidence for multiple memory systems, J. Neurosci., 9, 1465, 10.1523/JNEUROSCI.09-05-01465.1989 Park, 1982, Spatial memory in older adults: effects of intentionality, J. Gerontol., 37, 330, 10.1093/geronj/37.3.330 Park, 1990, Effects of distinctive context on memory for objects and their locations in young and elderly adults, Psychol. Aging, 5, 250, 10.1037/0882-7974.5.2.250 Parsons, 1998, Modulation of NMDA receptors by glycine—introduction to some basic aspects and recent developments, Amino Acids, 14, 207, 10.1007/BF01345264 Pelleymounter, 1987, Spatial learning impairments in aged rats trained with a salient configuration of stimuli, Psychobiology, 15, 248, 10.3758/BF03327276 Perlmutter, 1981, Spatial and temporal memory in 20 and 60 year olds, J. Gerontol., 36, 59, 10.1093/geronj/36.1.59 Peters, 1996, Neurobiological bases of age-related cognitive decline in the rhesus monkey, J. Neuropathol. Exp. Neurol., 55, 861, 10.1097/00005072-199608000-00001 Pezdek, 1983, Memory for items and their spatial locations by young and elderly adults, Dev. Psychol., 19, 895, 10.1037/0012-1649.19.6.895 Pico, 1985, During stepwise cue deletion, rat place behaviors correlate with place unit responses, Brain Res., 330, 369, 10.1016/0006-8993(85)90700-0 Pigott, 1993, Memory for different aspects of complex visual scenes after unilateral temporal- or frontal-lobe resection, Neuropsychologia, 31, 1, 10.1016/0028-3932(93)90076-C Pitler, 1990, Aging-related prolongation of calcium spike duration in rat hippocampal slice neurons, Brain Res., 508, 1, 10.1016/0006-8993(90)91109-T Pitsikas, 1992, Deterioration of spatial and nonspatial reference and working memory in aged rats: protective effect of life-long caloric restriction, Neurobiol. Aging, 13, 369, 10.1016/0197-4580(92)90110-J Pitsikas, 1992, Effect of lifelong hypocaloric diet on discrete memory of the senescent rat, Aging (Milan), 3, 147 Potegal, 1969, Role of the caudate nucleus in spatial orientation of rats, J. Comp. Physiol. Psychol., 69, 756, 10.1037/h0028168 Potier, 1992, Alterations in the properties of hippocampal pyramidal neurons in the aged rat, Neuroscience, 48, 793, 10.1016/0306-4522(92)90267-6 Potier, 1993, Age-related alterations in the properties of hippocampal pyramidal neurons among rat strains, Neurobiol. Aging, 14, 17, 10.1016/0197-4580(93)90016-5 Potier, 2000, NMDA receptor activation in the aged rat hippocampus, Exp. Gerontol., 35, 1185, 10.1016/S0531-5565(00)00122-4 Power, 1997, Enhanced synaptic transmission in CA1 hippocampus after eyeblink conditioning, J. Neurophysiol., 78, 1184, 10.1152/jn.1997.78.2.1184 Power, 2002, Age-related enhancement of the slow outward calcium-activated potassium current in hippocampal CA1 pyramidal neurons in vitro, J. Neurosci., 22, 7234, 10.1523/JNEUROSCI.22-16-07234.2002 Quirk, G.J., R.U., M., J.L., K., 1990. The firing of hippocampal place cells in the dark depends on the rat’s recent experience. J. Neurosci. 10, 2008–2017. Rao, 1993, Effects of age on l-glutamate-induced depolarization in three hippocampal subfields, Neurobiol. Aging, 14, 27, 10.1016/0197-4580(93)90017-6 Rao, 1994, Age-related decrease in the NMDA-mediated EPSP in FD, Soc. Neurosci. Abstr., 20, 1207 Rapp, 1998, Representational organization in the aged hippocampus, Hippocampus, 8, 432, 10.1002/(SICI)1098-1063(1998)8:5<432::AID-HIPO2>3.0.CO;2-A Rapp, 1996, Preserved neuron number in the hippocampus of aged rats with spatial learning deficits, Proc. Natl. Acad. Sci. U.S.A., 93, 9926, 10.1073/pnas.93.18.9926 Rapp, 1987, An evaluation of spatial information processing in aged rats, Behav. Neurosci., 101, 3, 10.1037/0735-7044.101.1.3 Rapp, 1997, Impaired spatial information processing in aged monkeys with preserved recognition memory, NeuroReport, 8, 1923, 10.1097/00001756-199705260-00026 Rasmussen, 1996, Memory impaired aged rats: no loss of principal hippocampal and subicular neurons, Neurobiol. Aging, 17, 143, 10.1016/0197-4580(95)02032-2 Read, 1987, Neuropsychological assessment of memory in the elderly, Can. J. Psychol., 41, 158, 10.1037/h0084358 Redish, A.D., 1999. Beyond the Cognitive Map: From Place Cells to Episodic Memory. MIT Press, Cambridge. Redish, 1997, Cognitive maps beyond the hippocampus, Hippocampus, 7, 1, 10.1002/(SICI)1098-1063(1997)7:1<15::AID-HIPO3>3.0.CO;2-6 Redish, 1998, The role of the hippocampus in solving the Morris water maze, Neural Comput., 10, 73, 10.1162/089976698300017908 Redish, 1998, Reconciling Barnes et al. (1997) and Tanila et al. (1997a,b), Hippocampus, 8, 438, 10.1002/(SICI)1098-1063(1998)8:5<438::AID-HIPO4>3.0.CO;2-Z Redish, 2000, Dynamics of hippocampal ensemble activity realignment: time vs. space, J. Neurosci., 20, 9298, 10.1523/JNEUROSCI.20-24-09298.2000 Reynolds, 1989, Diminished calcium currents in aged hippocampal dentate gyrus granule neurones, Brain Res., 479, 384, 10.1016/0006-8993(89)91646-6 Rioult-Pedotti, 1998, Strengthening of horizontal cortical connections following skill learning, Nat. Neurosci., 1, 230, 10.1038/678 Rioult-Pedotti, 2000, Learning-induced LTP in neocortex, Science, 290, 533, 10.1126/science.290.5491.533 Robinson, 1994, Estrogen replacement therapy and memory in older women, J. Am. Geriatr. Soc., 42, 919, 10.1111/j.1532-5415.1994.tb06580.x Rogan, 1997, Fear conditioning induces associative long-term potentiation in the amygdala, Nature, 390, 604, 10.1038/37601 Rolls, E.T., 1989. The representation and storage of information in neural networks in the primate cerebral cortex and hippocampus. In: Durbin, R. Miall, C., Michinson, G. (Eds.), The Computing Neuron. Addison-Wesley, New York, pp. 125–159. Ronn, 2000, The neural cell adhesion molecule in synaptic plasticity and ageing, Int. J. Dev. Neurosci., 18, 193, 10.1016/S0736-5748(99)00088-X Rosenbaum, 2000, Remote spatial memory in an amnesic person with extensive bilateral hippocampal lesions, Nat. Neurosci., 3, 1044, 10.1038/79867 Rosenzweig, E.S., Redish, A.D., McNaughton, B.L., Barnes, C.A., 2003. Hippocampal map realignment and spatial learning. Nature Neuroscience, in press. Rosenzweig, 1997, Role of temporal summation in age-related LTP-induction deficits, Hippocampus, 7, 549, 10.1002/(SICI)1098-1063(1997)7:5<549::AID-HIPO10>3.0.CO;2-0 Rosenzweig, 2002, Making room for new memories, Nat. Neurosci., 5, 6, 10.1038/nn0102-6 Rotenberg, 2000, Parallel instabilities of long-term potentiation, place cells, and learning caused by decreased protein kinase A activity, J. Neurosci., 20, 8096, 10.1523/JNEUROSCI.20-21-08096.2000 Samsonovich, 1997, Path integration and cognitive mapping in a continuous attractor neural network model, J. Neurosci., 17, 5900, 10.1523/JNEUROSCI.17-15-05900.1997 Sandin, 1990, Aging and cognition: facilitation of recent memory in aged nonhuman primates by nimodipine, Neurobiol. Aging, 11, 573, 10.1016/0197-4580(90)90120-O Sapolsky, R.M., 1987. Protecting the injured hippocampus by attenuating glucocorticoid secretion. In: Davies, P., Finch, C.E. (Eds.), Molecular Neuropathology of Aging. Cold Spring Harbor Laboratory, New York, pp. 191–204. Sapolsky, 1985, Prolonged glucocoticoid exposure reduces hippocampal neuron number: implications for aging, J. Neurosci., 5, 1222, 10.1523/JNEUROSCI.05-05-01222.1985 Saucier, 1995, Spatial learning without NMDA receptor-dependent long-term potentiation, Nature, 378, 186, 10.1038/378186a0 Save, 1998, Spatial firing of hippocampal place cells in blind rats, J. Neurosci., 18, 1818, 10.1523/JNEUROSCI.18-05-01818.1998 Save, 2000, Contribution of multiple sensory information to place field stability in hippocampal place cells, Hippocampus, 10, 64, 10.1002/(SICI)1098-1063(2000)10:1<64::AID-HIPO7>3.0.CO;2-Y Scoville, 1957, Loss of recent memory after bilateral hippocampal lesions, J. Neurol. Neurosurg. Psychiatry, 20, 11, 10.1136/jnnp.20.1.11 Scriabine, 1989, Pharmacological basis for the use of nimodipine in central nervous system disorders, FASEB J., 3, 1799, 10.1096/fasebj.3.7.2565839 Segal, 1982, Changes in neurotransmitter actions in the aged rat hippocampus, Neurobiol. Aging, 3, 121, 10.1016/0197-4580(82)90007-0 Sejnowski, 1977, Storing covariance with nonlinearly interacting neurons, J. Math. Biol., 4, 303, 10.1007/BF00275079 Shankar, 1998, Aging differentially alters forms of long-term potentiation in rat hippocampal area CA1, J. Neurophysiol., 79, 334, 10.1152/jn.1998.79.1.334 Shapiro, 1989, Intrahippocampal grafts of fetal basal forebrain tissue alter place fields in the hippocampus of rats with fimbria-fornix lesions, Neuroscience, 32, 1, 10.1016/0306-4522(89)90103-6 Sharp, 1989, Exploration dependent modulation of evoked responses in facia dentata: fundamental observations and time course, Psychobiology, 17, 257, 10.1007/BF03337777 Sharp, 1995, Influences of vestibular and visual motion information on the spatial firing patterns of hippocampal place cells, J. Neurosci., 15, 173, 10.1523/JNEUROSCI.15-01-00173.1995 Sharps, 1987, Memory for object locations in young and elderly adults, J. Gerontol., 42, 336, 10.1093/geronj/42.3.336 Shen, 1996, Age-related decrease in cholinergic synaptic transmission in three hippocampal subfields, Neurobiol. Aging, 17, 439, 10.1016/0197-4580(96)00020-6 Shen, 1997, The effect of aging on experience-dependent plasticity of hippocampal place cells, J. Neurosci., 17, 6769, 10.1523/JNEUROSCI.17-17-06769.1997 Sherwin, 1997, Estrogen effects on cognition in menopausal women, Neurology, 48, S21, 10.1212/WNL.48.5_Suppl_7.21S Shi, 1999, Rapid spine delivery and redistribution of AMPA receptors after synaptic NMDA receptor activation, Science, 284, 1811, 10.1126/science.284.5421.1811 Shimada, 1997, N-Methyl-d-aspartate receptor binding in brains of rats at different ages, Neurobiol. Aging, 18, 329, 10.1016/S0197-4580(97)80315-6 Simpkins, 1994, The potential role for estrogen replacement therapy in the treatment of the cognitive decline and neurodegeneration associated with Alzheimer’s disease, Neurobiol. Aging, 15, S195, 10.1016/0197-4580(94)90205-4 Smith, 1988, Recall of spatial location by the amnesic patient H.M, Brain Cogn., 7, 178, 10.1016/0278-2626(88)90028-0 Smith, 1999, Circuit and morphological specificity of synaptic change in the aged hippocampal formation, Neurobiol. Aging, 20, 357 Smith, 2000, Effect of age on burst firing characteristics of rat hippocampal pyramidal cells, NeuroReport, 11, 3865, 10.1097/00001756-200011270-00052 Smith, 2000, Circuit-specific alterations in hippocampal synaptophysin immunoreactivity predict spatial learning impairment in aged rats, J. Neurosci., 20, 6587, 10.1523/JNEUROSCI.20-17-06587.2000 Squire, 1992, Memory and the hippocampus: a synthesis from findings with rats, monkeys, and humans, Psychol. Rev., 99, 195, 10.1037/0033-295X.99.2.195 Stäubli, 1996, Proactive and retrograde effects on LTP produced by theta pulse stimulation: mechanisms and characteristics of LTP reversal in vitro, Learn. Mem., 3, 96, 10.1101/lm.3.2-3.96 Stäubli, 1996, Factors regulating the reversibility of long-term potentiation, J. Neurosci., 16, 853, 10.1523/JNEUROSCI.16-02-00853.1996 Stäubli, 1996, The induction of homo- vs. heterosynaptic LTD in area CA1 of hippocampal slices from adult rats, Brain Res., 714, 169, 10.1016/0006-8993(95)01523-X Stäubli, 1987, Stable hippocampal long-term potentiation elicited by ‘theta’ pattern stimulation, Brain Res., 435, 227, 10.1016/0006-8993(87)91605-2 Stäubli, 1990, Stable depression of potentiated synaptic responses in the hippocampus with 1–5 Hz stimulation, Brain Res., 513, 113, 10.1016/0006-8993(90)91096-Y Stäubli, 1997, Studies on long-term depression in area CA1 of the anesthetized and freely moving rat, J. Neurosci., 17, 4820, 10.1523/JNEUROSCI.17-12-04820.1997 Stäubli, 1989, Antagonism of NMDA receptors impairs acquisition but not retention of olfactory memory, Behav. Neurosci., 103, 54, 10.1037/0735-7044.103.1.54 Stefanacci, 2000, Profound amnesia after damage to the medial temporal lobe: a neuroanatomical and neuropsychological profile of patient E.P, J. Neurosci., 20, 7024, 10.1523/JNEUROSCI.20-18-07024.2000 Sterio, 1984, The unbiased estimation of number and sizes of arbitrary particles using the disector, Brain Res., 134, 127 Strack, 1997, Differential inactivation of postsynaptic density-associated and soluble Ca2+/calmodulin-dependent protein kinase II by protein phosphatases 1 and 2A, J. Neurochem., 68, 2119, 10.1046/j.1471-4159.1997.68052119.x Straube, 1990, Dietary nimodipine improves associative learning in aging rabbits, Neurobiol. Aging, 11, 659, 10.1016/0197-4580(90)90033-V Sullivan, 1997, Ubiased estimation of possible age-related changes in total number of synapses in the hippocampal CA1 region of the rat, Soc. Neurosci. Abstr., 23, 1459 Tamaru, 1991, Age-related decreases of the N-methyl-d-aspartate receptor complex in the rat cerebral cortex and hippocampus, Brain Res., 542, 83, 10.1016/0006-8993(91)91001-H Tanila, 1997, Brain aging: changes in the nature of information coding by the hippocampus, J. Neurosci., 17, 5155, 10.1523/JNEUROSCI.17-13-05155.1997 Tanila, 1997, Brain aging: impaired coding of novel environmental cues, J. Neurosci., 17, 5167, 10.1523/JNEUROSCI.17-13-05167.1997 Teng, 1999, Memory for places learned long ago is intact after hippocampal damage, Nature, 400, 675, 10.1038/23276 Teyler, 1994, Multideterminant role of calcium in hippocampal synaptic platicity, Hippocampus, 4, 623, 10.1002/hipo.450040602 Thibault, 1996, Increase in single L-type calcium channels in hippocampal neurons during aging, Science, 272, 1017, 10.1126/science.272.5264.1017 Thibault, 2001, Elevated postsynaptic [Ca2+]i and L-type calcium channel activity in aged hippocampal neurons: relationship to impaired synaptic plasticity, J. Neurosci., 21, 9744, 10.1523/JNEUROSCI.21-24-09744.2001 Thiels, 1994, Excitatory stimulation during postsynaptic inhibition induces long-term depression in hippocampus in vivo, J. Neurophysiol., 72, 3009, 10.1152/jn.1994.72.6.3009 Thiels, 1996, NMDA receptor-dependent LTD in different subfields of hippocampus in vivo and in vitro, Hippocampus, 6, 43, 10.1002/(SICI)1098-1063(1996)6:1<43::AID-HIPO8>3.0.CO;2-8 Thiels, 1998, Transient and persistent increases in protein phosphatase activity during long-term depression in the adult hippocampus in vivo, Neuroscience, 86, 1023, 10.1016/S0306-4522(98)00135-3 Thomas, 1985, Visual memory: adult age difference in map recall and learning strategies, Exp. Aging Res., 11, 93, 10.1080/03610738508259286 Thompson, 1989, Place cells and silent cells in the hippocampus of freely moving rats, J. Neurosci., 9, 2382, 10.1523/JNEUROSCI.09-07-02382.1989 Thompson, 1990, Long-term stability of place-field activity of single units recorded from the dorsal hippocampus of freely behaving rats, Brain Res., 509, 299, 10.1016/0006-8993(90)90555-P Thompson, 1990, Nimodipine enhances spontaneous activity of hippocampal pyramidal neurons in aging rabbits at a dose that facilitates associative learning, Brain Res., 535, 119, 10.1016/0006-8993(90)91830-A Tielen, A.M., Mollevanger, W.J., Lopes da Silva, F.H., Hollander, C.F., 1983. Neuronal plasticity in hippocampal slices of extremely old rats. In: Gispen, W.H., Traber, J. (Eds.), Aging of the Brain. Elsevier, Amsterdam, pp. 73–84. Tomlinson, B.E., Henderson, G., 1976. Some quantitative cerebral findings in normal and demented old people. In: Terry, R.D., Gershon, S. (Eds.), Neurobiology of Aging. Raven Press, New York, pp. 183–204. Tonegawa, 1996, Hippocampal CA1-region-restricted knockout of NMDAR1 gene disrupts synaptic plasticity, place fields, and spatial learning, Cold Spring Harb. Symp. Quant. Biol., 61, 225, 10.1101/SQB.1996.061.01.025 Tonkiss, 1991, The competitive NMDA antagonist AP5, but not the non-competitive antagonist MK801, induces a delay-related impairment in spatial working memory in rats, Exp. Brain Res., 85, 349, 10.1007/BF00229412 Tonkiss, 1988, Intra-ventricular infusion of the NMDA antagonist AP5 impairs performance on a non-spatial operant DRL task in the rat, Exp. Brain Res., 73, 181, 10.1007/BF00279671 Touretzky, 1996, Theory of rodent navigation based on interacting representations of space, Hippocampus, 6, 247, 10.1002/(SICI)1098-1063(1996)6:3<247::AID-HIPO4>3.0.CO;2-K Tsien, 1996, Subregion- and cell type-restricted gene knockout in mouse brain, Cell, 87, 1317, 10.1016/S0092-8674(00)81826-7 Tsien, 1996, The essential role of hippocampal CA1 NMDA receptor dependent synaptic plasticity in spatial memory, Cell, 87, 1327, 10.1016/S0092-8674(00)81827-9 Tulving, 1998, Episodic and declarative memory: role of the hippocampus, Hippocampus, 8, 198, 10.1002/(SICI)1098-1063(1998)8:3<198::AID-HIPO2>3.0.CO;2-G Turner, 1991, Functional elongation of CA1 hippocampal neurons with aging in Fischer 344 rats, Neurobiol. Aging, 12, 201, 10.1016/0197-4580(91)90098-5 Uttl, 1993, Episodic spatial memory in adulthood, Psychol. Aging, 8, 257, 10.1037/0882-7974.8.2.257 van Gool, 1985, Spatial memory and visual evoked potentials in young and old rats after housing in an enriched environment, Behav. Neural Biol., 44, 454, 10.1016/S0163-1047(85)90880-5 van Pragg, 1999, Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus, Nat. Neurosci., 2, 266, 10.1038/6368 Vargha-Khadem, 1997, Differential effects of early hippocampal pathology on episodic and semantic memory, Science, 277, 376, 10.1126/science.277.5324.376 Vereker, 2000, The inhibitory effect of interleukin-1β on long-term potentiation is coupled with increased activity of stress-activated protein kinases, J. Neurosci., 20, 6811, 10.1523/JNEUROSCI.20-18-06811.2000 Villarreal, 2002, NMDA receptor antagonists sustain LTP and spatial memory: evidence for active processes mediating LTP decay, Nat. Neurosci., 5, 48, 10.1038/nn776 Vouimba, 2000, 17β-Estradiol suppresses expression of long-term depression in aged rats, Brain Res. Bull., 53, 783, 10.1016/S0361-9230(00)00377-4 Waddell, 1981, Effect of contextual organization on spatial memory of middle-aged and older women, Dev. Psychol., 17, 878, 10.1037/0012-1649.17.6.878 Wallace, 1980, Animal models of declining memory in the aged: short-term and spatial memory in the aged rat, J. Gerontol., 35, 355, 10.1093/geronj/35.3.355 Walsh, D., Krauss, I., Regnier, V., 1981. Spatial ability, environmental knowledge and environmental use. In: Liben, L., Patterson, A.H., Newcombe, N. (Eds.), Spatial Representation and Behavior Across the Life Span. Academic Press, New York, pp. 321–357. Wang, 1999, Priming-induced shift in synaptic plasticity in the rat hippocampus, J. Neurophysiol., 82, 2024, 10.1152/jn.1999.82.4.2024 Weber, 1978, Cognitive maps of environmental knowledge and preference in nursing home patients, Exp. Aging Res., 4, 157, 10.1080/03610737808257141 Wenk, 2000, Regional changes in the hippocampal density of AMPA and NMDA receptors across the lifespan of the rat, Brain Res., 885, 1, 10.1016/S0006-8993(00)02792-X Wenk, 1991, Loss of NMDA, but not GABA-A, binding in the brains of aged rats and monkeys, Neurobiol. Aging, 12, 93, 10.1016/0197-4580(91)90047-N West, 1993, Regionally specific loss of neurons in the aging human hippocampus, Neurobiol. Aging, 14, 287, 10.1016/0197-4580(93)90113-P West, 1993, New stereological methods for counting neurons, Neurobiol. Aging, 14, 275, 10.1016/0197-4580(93)90112-O West, 1993, Preserved hippocampal cell number in aged monkeys with recognition memory deficits, Soc. Neurosci. Abstr., 19, 599 Whishaw, 1995, Rats with fimbria-fornix lesions display a place response in a swimming pool: a dissociation between getting there and knowing where, J. Neurosci., 15, 5779, 10.1523/JNEUROSCI.15-08-05779.1995 Wigström, 1986, Hippocampal long-term potentiation is induced by pairing single afferent volleys with intracellularly injected depolarizing current pulses, Acta Physiol. Scand., 126, 317, 10.1111/j.1748-1716.1986.tb07822.x Wilkniss, 1997, Age-related differences in an ecologically-based study of route learning, Psychol. Aging, 12, 372, 10.1037/0882-7974.12.2.372 Wilson, 1993, Dynamics of the hippocampal ensemble code for space, Science, 261, 1055, 10.1126/science.8351520 Wilson, 1997, Synaptic plasticity, place cells and spatial memory: study with second generation knockouts, Trends Neurosci., 20, 102, 10.1016/S0166-2236(96)01023-5 Wise, 2001, Estrogens: trophic and protective factors in the adult brain, Front. Neuroendocrinol., 22, 33, 10.1006/frne.2000.0207 Xu, 1998, Spatial exploration induces a persistent reversal of long-term potentiation in rat hippocampus, Nature, 394, 891, 10.1038/29783 Yau, 1996, Decreased NGFI-A gene expression in the hippocampus of cognitively impaired aged rats, Brain Res. Mol. Brain Res., 42, 354, 10.1016/S0169-328X(96)00220-3 Zelinski, 1988, Young and older adults’ use of context in spatial memory, Psychol. Aging, 3, 99, 10.1037/0882-7974.3.1.99 Zola-Morgan, 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, 2950, 10.1523/JNEUROSCI.06-10-02950.1986