Dissecting mechanisms of brain aging by studying the intrinsic excitability of neurons

Frontiers in Aging Neuroscience

Volumn 7, Issue JAN, 2015, Pages

  Rizzo, Valerio ^a   Richman, Jeffrey ^a   Puthanveettil, Sathyanarayanan V ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

Author keywords

Action potential; Aging; Electrophysiology; Single neuron; Synaptic transmission

Indexed keywords

NEUROTRANSMITTER RECEPTOR;

ACTION POTENTIAL; AFTERHYPERPOLARIZATION; AGING; BRAIN FUNCTION; CHOLINERGIC NERVE CELL; DENDRITE; DENDRITIC SPINE; HUMAN; NERVE CELL; NERVE CONDUCTION; NERVE EXCITABILITY; NONHUMAN; PRIMARY SOMATOSENSORY CORTEX; SENSORY GANGLION; SHORT SURVEY; SYNAPTIC TRANSMISSION;

EID: 84922460589     PISSN: None     EISSN: 16634365     Source Type: Journal    
DOI: 10.3389/fnagi.2014.00337     Document Type: Short Survey

References (105)

1. Akhmedov, K., Rizzo, V., Kadakkuzha, B. M., Carter, C. J., Magoski, N. S., Capo, T. R., et al. (2013). Decreased response to acetylcholine during aging of aplysia neuron R15. PLoS One 8:e84793. doi: 10.1371/journal.pone.0084793
2. Albert, M. (1993). Neuropsychological and neurophysiological changes in healthy adult humans across the age range. Neurobiol. Aging 14, 623-625. doi: 10.1016/0197-4580(93)90049-h
3. Aston-Jones, G., Rogers, J., Shaver, R. D., Dinan, T. G., and Moss, D. E. (1985). Age-impaired impulse flow from nucleus basalis to cortex. Nature 318, 462-464. doi: 10.1038/318462a0
4. Ball, M. J. (1977). Neuronal loss, neurofibrillary tangles and granulovacuolar degeneration in the hippocampus with ageing and dementia. A quantitative study. Acta Neuropathol. 37, 111-118. doi: 10.1007/bf00692056
5. Boiko, T., Rasband, M. N., Levinson, S. R., Caldwell, J. H., Mandel, G., Trimmer, J. S., et al. (2001). Compact myelin dictates the differential targeting of two sodium channel isoforms in the same axon. Neuron 30, 91-104. doi: 10.1016/s0896-6273(01)00265-3
6. Bond, C. T., Herson, P. S., Strassmaier, T., Hammond, R., Stackman, R., Maylie, J., et al. (2004). Small conductance Ca2+-activated K+ channel knock-out mice reveal the identity of calcium-dependent afterhyperpolarization currents. J. Neurosci. 24, 5301-5306. doi: 10.1523/jneurosci.0182-04.2004
7. Branch, S. Y., Sharma, R., and Beckstead, M. J. (2014). Aging decreases L-type calcium channel currents and pacemaker firing fidelity in substantia nigra dopamine neurons. J. Neurosci. 34, 9310-9318. doi: 10.1523/JNEUROSCI.4228-13.2014
8. Brewer, L. D., Dowling, A. L., Curran-Rauhut, M. A., Landfield, P. W., Porter, N. M., and Blalock, E. M. (2009). Estradiol reverses a calcium-related biomarker of brain aging in female rats. J. Neurosci. 29, 6058-6067. doi: 10.1523/JNEUROSCI.5253-08.2009
9. Brizzee, K. R., and Knox, C. (1980). The aging process in the neuron. Adv. Exp. Med. Biol. 129, 71-98. doi: 10.1007/978-1-4684-3734-8_9
10. Brody, H. (1955). Organization of the cerebral cortex. III. A study of aging in the human cerebral cortex. J. Comp. Neurol. 102, 511-516. doi: 10.1002/cne.901020206
11. Burke, S. N., and Barnes, C. A. (2006). Neural plasticity in the ageing brain. Nat. Rev. Neurosci. 7, 30-40. doi: 10.1038/nrn1809
12. Caetano, M. S., Horst, N. K., Harenberg, L., Liu, B., Arnsten, A. F., and Laubach, M. (2012). Lost in transition: aging-related changes in executive control by the medial prefrontal cortex. J. Neurosci. 32, 3765-3777. doi: 10.1523/JNEUROSCI.6011-11.2012
13. Campbell, L. W., Hao, S. Y., Thibault, O., Blalock, E. M., and Landfield, P. W. (1996). Aging changes in voltage-gated calcium currents in hippocampal CA1 neurons. J. Neurosci. 16, 6286-6295.
14. Chang, Y.-M., Rosene, D. L., Killiany, R. J., Mangiamele, L. A., and Luebke, J. I. (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, 409-418. doi: 10.1093/cercor/bhh144
15. Chase, M. H., Morales, F. R., Boxer, P. A., and Fung, S. J. (1985). Aging of motoneurons and synaptic processes in the cat. Exp. Neurol. 90, 471-478. doi: 10.1016/0014-4886(85)90035-4
16. Chen, K. S., Masliah, E., Mallory, M., and Gage, F. H. (1995). Synaptic loss in cognitively impaired aged rats is ameliorated by chronic human nerve growth factor infusion. Neuroscience 68, 19-27. doi: 10.1016/0306-4522(95)00099-5
17. Chiu, S. Y. (1991). Functions and distribution of voltage-gated sodium and potassium channels in mammalian Schwann cells. Glia 4, 541-558. doi: 10.1002/glia.440040602
18. Coleman, P. D., and Flood, D. G. (1987). Neuron numbers and dendritic extent in normal aging and Alzheimer's disease. Neurobiol. Aging 8, 521-545. doi: 10.1016/0197-4580(87)90127-8
19. de Brabander, J. M., Kramers, R. J., and Uylings, H. B. (1998). Layer-specific dendritic regression of pyramidal cells with ageing in the human prefrontal cortex. Eur. J. Neurosci. 10, 1261-1269. doi: 10.1046/j.1460-9568.1998.00137.x
20. Disterhoft, J. F., and Oh, M. M. (2006). Learning, aging and intrinsic neuronal plasticity. Trends Neurosci. 29, 587-599. doi: 10.1016/j.tins.2006.08.005
21. Disterhoft, J. F., and Oh, M. M. (2007). Alterations in intrinsic neuronal excitability during normal aging. Aging Cell 6, 327-336. doi: 10.1111/j.1474-9726.2007.00297.x
22. Disterhoft, J. F., Thompson, L. T., Moyer, J. R. Jr., and Mogul, D. J. (1996). Calcium-dependent afterhyperpolarization and learning in young and aging hippocampus. Life Sci. 59, 413-420. doi: 10.1016/0024-3205(96)00320-7
23. Dodge, F. A., and Cooley, J. W. (1973). Action potential of the Motorneuron. IBM J. Res. Dev. 17, 219-229. doi: 10.1147/rd.173.0219
24. Driver, C., Georgiou, A., and Georgiou, G. (2004). The contribution by mitochondrially induced oxidative damage to aging in Drosophila melanogaster. Biogerontology 5, 185-192. doi: 10.1023/b:bgen.0000031156.75376.e3
25. Duan, H., Wearne, S. L., Rocher, A. B., Macedo, A., Morrison, J. H., and Hof, P. R. (2003). Age-related dendritic and spine changes in corticocortically projecting neurons in macaque monkeys. Cereb. Cortex 13, 950-961. doi: 10.1093/cercor/13.9.950
26. Erraji-Benchekroun, L., Underwood, M. D., Arango, V., Galfalvy, H., Pavlidis, P., Smyrniotopoulos, P., et al. (2005). Molecular aging in human prefrontal cortex is selective and continuous throughout adult life. Biol. Psychiatry 57, 549-558. doi: 10.1016/j.biopsych.2004.10.034
27. Fieber, L. A., Carlson, S. L., Capo, T. R., and Schmale, M. C. (2010). Changes in D-aspartate ion currents in the Aplysia nervous system with aging. Brain Res. 1343, 28-36. doi: 10.1016/j.brainres.2010.05.001
28. Foehring, R. C., and Surmeier, D. J. (1993). Voltage-gated potassium currents in acutely dissociated rat cortical neurons. J. Neurophysiol. 70, 51-63.
29. Foster, T. C. (2007). Calcium homeostasis and modulation of synaptic plasticity in the aged brain. Aging Cell 6, 319-325. doi: 10.1111/j.1474-9726.2007.00283.x
30. Gant, J. C., Sama, M. M., Landfield, P. W., and Thibault, O. (2006). Early and simultaneous emergence of multiple hippocampal biomarkers of aging is mediated by Ca2+-induced Ca2+ release. J. Neurosci. 26, 3482-3490. doi: 10.1523/jneurosci.4171-05.2006
31. Gazzaley, A. H., Thakker, M. M., Hof, P. R., and Morrison, J. H. (1997). Preserved number of entorhinal cortex layer II neurons in aged macaque monkeys. Neurobiol. Aging 18, 549-553. doi: 10.1016/s0197-4580(97)00112-7
32. Giese, K. P., Storm, J. F., Reuter, D., Fedorov, N. B., Shao, L. R., Leicher, T., et al. (1998). Reduced K+ channel inactivation, spike broadening and after-hyperpolarization in Kvbeta1.1-deficient mice with impaired learning. Learn. Mem. 5, 257-273.
33. Gu, N., Vervaeke, K., Hu, H., and Storm, J. F. (2005). Kv7/KCNQ/M and HCN/h, but not KCa2/SK channels, contribute to the somatic medium after-hyperpolarization and excitability control in CA1 hippocampal pyramidal cells. J. Physiol. 566, 689-715. doi: 10.1113/jphysiol.2005.086835
34. Harley, P. R. (1975). A possible age-related decrement in the conduction velocity of Aplysia neuron R2. Experientia 31, 901-902. doi: 10.1007/bf02358840
35. Hickmott, P., and Dinse, H. (2013). Effects of aging on properties of the local circuit in rat primary somatosensory cortex (S1) in vitro. Cereb. Cortex 23, 2500-2513. doi: 10.1093/cercor/bhs248
36. Hinman, J. D., Peters, A., Cabral, H., Rosene, D. L., Hollander, W., Rasband, M. N., et al. (2006). Age-related molecular reorganization at the node of Ranvier. J. Comp. Neurol. 495, 351-362. doi: 10.1002/cne.20886
37. Hsu, K. S., Huang, C. C., Liang, Y. C., Wu, H. M., Chen, Y. L., Lo, S. W., et al. (2002). Alterations in the balance of protein kinase and phosphatase activities and age-related impairments of synaptic transmission and long-term potentiation. Hippocampus 12, 787-802. doi: 10.1002/hipo.10032
38. Hua, T., Li, X., He, L., Zhou, Y., Wang, Y., and Leventhal, A. G. (2006). Functional degradation of visual cortical cells in old cats. Neurobiol. Aging 27, 155-162. doi: 10.1016/j.neurobiolaging.2004.11.012
39. Iwamoto, M., Hagishita, T., Shoji-Kasai, Y., Ando, S., and Tanaka, Y. (2004). Age-related changes in the levels of voltage-dependent calcium channels and other synaptic proteins in rat brain cortices. Neurosci. Lett. 366, 277-281. doi: 10.1016/j.neulet.2004.05.048
40. Jacobs, B., Driscoll, L., and Schall, M. (1997). Life-span dendritic and spine changes in areas 10 and 18 of human cortex: a quantitative Golgi study. J. Comp. Neurol. 386, 661-680. doi: 10.1002/(sici)1096-9861(19971006)386:4<661::aid-cne11>3.0.co;2-n
41. Kadakkuzha, B. M., Akhmedov, K., Capo, T. R., Carvalloza, A. C., Fallahi, M., and Puthanveettil, S. V. (2013). Age-associated bidirectional modulation of gene expression in single identified R15 neuron of Aplysia. BMC Genomics 14:880. doi: 10.1186/1471-2164-14-880
42. Kempsell, A. T., and Fieber, L. A. (2014). Behavioral aging is associated with reduced sensory neuron excitability in Aplysia californica. Front. Aging Neurosci. 6:84. doi: 10.3389/fnagi.2014.00084
43. Kerr, D. S., Campbell, L. W., Hao, S. Y., and Landfield, P. W. (1989). Corticosteroid modulation of hippocampal potentials: increased effect with aging. Science 245, 1505-1509. doi: 10.1126/science.2781293
44. Keuker, J. I., Luiten, P. G., and Fuchs, E. (2003). Preservation of hippocampal neuron numbers in aged rhesus monkeys. Neurobiol. Aging 24, 157-165. doi: 10.1016/s0197-4580(02)00062-3
45. Korngreen, A., and Sakmann, B. (2000). Voltage-gated K+ channels in layer 5 neocortical pyramidal neurones from young rats: subtypes and gradients. J. Physiol. 525, 621-639. doi: 10.1111/j.1469-7793.2000.00621.x
46. Kumar, A., Bodhinathan, K., and Foster, T. C. (2009). Susceptibility to calcium dysregulation during brain aging. Front. Aging Neurosci. 1:2. doi: 10.3389/neuro.24.002.2009
47. Kumar, A., and Foster, T. C. (2004). Enhanced long-term potentiation during aging is masked by processes involving intracellular calcium stores. J. Neurophysiol. 91, 2437-2444. doi: 10.1152/jn.01148.2003
48. Kumar, A., and Foster, T. C. (2007). "Neurophysiology of old neurons and synapses," in Brain Aging: Models, Methods and Mechanisms, ed D. R. Riddle (Boca Raton, FL: CRC Press), Section III, Chapter 10.
49. Lancaster, B., and Adams, P. R. (1986). Calcium-dependent current generating the afterhyperpolarization of hippocampal neurons. J. Neurophysiol. 55, 1268-1282.
50. Lancaster, B., and Nicoll, R. A. (1987). Properties of two calcium-activated hyperpolarizations in rat hippocampal neurones. J. Physiol. 389, 187-203.
51. Landfield, P. W., and Pitler, T. A. (1984). Prolonged Ca2+-dependent afterhyperpolarizations in hippocampal neurons of aged rats. Science 226, 1089-1092. doi: 10.1126/science.6494926
52. Leventhal, A. G., Wang, Y., Pu, M., Zhou, Y., and Ma, Y. (2003). GABA and its agonists improved visual cortical function in senescent monkeys. Science 300, 812-815. doi: 10.1126/science.1082874
53. Lu, C. B., Hamilton, J. B., Powell, A. D., Toescu, E. C., and Vreugdenhil, M. (2011). Effect of ageing on CA3 interneuron sAHP and gamma oscillations is activity-dependent. Neurobiol. Aging 32, 956-965. doi: 10.1016/j.neurobiolaging.2009.05.006
54. Luebke, J. I., and Chang, Y. M. (2007). Effects of aging on the electrophysiological properties of layer 5 pyramidal cells in the monkey prefrontal cortex. Neuroscience 150, 556-562. doi: 10.1016/j.neuroscience.2007.09.042
55. Luebke, J. I., Chang, Y. M., Moore, T. L., and Rosene, D. L. (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, 277-288. doi: 10.1016/j.neuroscience.2004.01.035
56. Luebke, J. I., Medalla, M., Amatrudo, J. M., Weaver, C. M., Crimins, J. L., Hunt, B., et al. (2013). Age-Related changes to layer 3 pyramidal cells in the rhesus monkey visual cortex. Cereb. Cortex doi: 10.1093/cercor/bht336. [Epub ahead of print].
57. Luebke, J. I., and Rosene, D. L. (2003). Aging alters dendritic morphology, input resistance and inhibitory signaling in dentate granule cells of the rhesus monkey. J. Comp. Neurol. 460, 573-584. doi: 10.1002/cne.10668
58. Maccaferri, G., Mangoni, M., Lazzari, A., and DiFrancesco, D. (1993). Properties of the hyperpolarization-activated current in rat hippocampal CA1 pyramidal cells. J. Neurophysiol. 69, 2129-2136.
59. Madison, D. V., and Nicoll, R. A. (1984). Control of the repetitive discharge of rat CA 1 pyramidal neurones in vitro. J. Physiol. 354, 319-331.
60. Matthews, E. A., Linardakis, J. M., and Disterhoft, J. F. (2009). The fast and slow afterhyperpolarizations are differentially modulated in hippocampal neurons by aging and learning. J. Neurosci. 29, 4750-4755. doi: 10.1523/JNEUROSCI.0384-09.2009
61. Merrill, D. A., Chiba, A. A., and Tuszynski, M. H. (2001). Conservation of neuronal number and size in the entorhinal cortex of behaviorally characterized aged rats. J. Comp. Neurol. 438, 445-456. doi: 10.1002/cne.1327
62. Merrill, D. A., Roberts, J. A., and Tuszynski, M. H. (2000). Conservation of neuron number and size in entorhinal cortex layers II, III and V/VI of aged primates. J. Comp. Neurol. 422, 396-401. doi: 10.1002/1096-9861(20000703)422:3<396::aid-cne6>3.0.co;2-r
63. Morales, F. R., Boxer, P. A., Fung, S. J., and Chase, M. H. (1987). Basic electrophysiological properties of spinal cord motoneurons during old age in the cat. J. Neurophysiol. 58, 180-194.
64. Moroz, L. L., and Kohn, A. B. (2010). Do different neurons age differently? Direct genome-wide analysis of aging in single identified cholinergic neurons. Front. Aging Neurosci. 2:6. doi: 10.3389/neuro.24.006.2010
65. Moyer, J. R. Jr., Power, J. M., Thompson, L. T., and Disterhoft, J. F. (2000). Increased excitability of aged rabbit CA1 neurons after trace eyeblink conditioning. J. Neurosci. 20, 5476-5482.
66. Moyer, J. R. Jr., Thompson, L. T., Black, J. P., and Disterhoft, J. F. (1992). Nimodipine increases excitability of rabbit CA1 pyramidal neurons in an age- and concentration-dependent manner. J. Neurophysiol. 68, 2100-2109.
67. Need, A. C., Irvine, E. E., and Giese, K. P. (2003). Learning and memory impairments in Kv beta 1.1-null mutants are rescued by environmental enrichment or ageing. Eur. J. Neurosci. 18, 1640-1644. doi: 10.1046/j.1460-9568.2003.02889.x
68. Oh, M. M., Oliveira, F. A., and Disterhoft, J. F. (2010). Learning and aging related changes in intrinsic neuronal excitability. Front. Aging Neurosci. 2:2. doi: 10.3389/neuro.24.002.2010
69. Page, T. L., Einstein, M., Duan, H., He, Y., Flores, T., Rolshud, D., et al. (2002). Morphological alterations in neurons forming corticocortical projections in the neocortex of aged Patas monkeys. Neurosci. Lett. 317, 37-41. doi: 10.1016/s0304-3940(01)02428-4
70. Pakkenberg, B., and Gundersen, H. J. (1997). Neocortical neuron number in humans: effect of sex and age. J. Comp. Neurol. 384, 312-320. doi: 10.1002/(sici)1096-9861(19970728)384:2<312::aid-cne10>3.0.co;2-k
71. Peters, A. (2002). The effects of normal aging on myelin and nerve fibers: a review. J. Neurocytol. 31, 581-593. doi: 10.1023/A:1025731309829
72. Peters, A., Leahu, D., Moss, M. B., and McNally, K. J. (1994). The effects of aging on area 46 of the frontal cortex of the rhesus monkey. Cereb. Cortex 4, 621-635. doi: 10.1093/cercor/4.6.621
73. Peters, A., Rosene, D. L., Moss, M. B., Kemper, T. L., Abraham, C. R., Tigges, J., et al. (1996). Neurobiological bases of age-related cognitive decline in the rhesus monkey. J. Neuropathol. Exp. Neurol. 55, 861-874. doi: 10.1097/00005072-199608000-00001
74. Peters, A., Sethares, C., and Killiany, R. J. (2001). Effects of age on the thickness of myelin sheaths in monkey primary visual cortex. J. Comp. Neurol. 435, 241-248. doi: 10.1002/cne.1205
75. Peters, A., Sethares, C., and Moss, M. B. (1998). The effects of aging on layer 1 in area 46 of prefrontal cortex in the rhesus monkey. Cereb. Cortex 8, 671-684. doi: 10.1093/cercor/8.8.671
76. Post-Munson, D. J., Lum-Ragan, J. T., Mahle, C. D., and Gribkoff, V. K. (1994). Reduced bicuculline response and GABAA agonist binding in aged rat hippocampus. Neurobiol. Aging 15, 629-633. doi: 10.1016/0197-4580(94)00057-3
77. Power, J. M., Wu, W. W., Sametsky, E., Oh, M. M., and Disterhoft, J. F. (2002). Age-related enhancement of the slow outward calcium-activated potassium current in hippocampal CA1 pyramidal neurons in vitro. J. Neurosci. 22, 7234-7243.
78. Randall, A. D., Booth, C., and Brown, J. T. (2012). Age-related changes to Na+ channel gating contribute to modified intrinsic neuronal excitability. Neurobiol. Aging 33, 2715-2720. doi: 10.1016/j.neurobiolaging.2011.12.030
79. Rapp, P. R., and Gallagher, M. (1996). Preserved neuron number in the hippocampus of aged rats with spatial learning deficits. Proc. Natl. Acad. Sci. U S A 93, 9926-9930. doi: 10.1073/pnas.93.18.9926
80. Rasband, M. N. (2004). It's "juxta" potassium channel! J. Neurosci. Res. 76, 749-757. doi: 10.1002/jnr.20073
81. Rasmussen, T., Schliemann, T., Sorensen, J. C., Zimmer, J., and West, M. J. (1996). Memory impaired aged rats: no loss of principal hippocampal and subicular neurons. Neurobiol. Aging 17, 143-147. doi: 10.1016/0197-4580(95)02032-2
82. Rogers, J., Zornetzer, S. F., and Bloom, F. E. (1981). Senescent pathology of cerebellum: Purkinje neurons and their parallel fiber afferents. Neurobiol. Aging 2, 15-25. doi: 10.1016/0197-4580(81)90054-3
83. Rosene, D., and Nicholson, T. (1999). "Neurotransmitter receptor changes in the hippocampus and cerebral cortex in normal aging," in Cerebral Cortex, eds A. Peters and J. Morrison (New York, Philadelphia: Springer), 111-128.
84. Sah, P. (1996). Ca(2+)-activated K+ currents in neurones: types, physiological roles and modulation. Trends Neurosci. 19, 150-154. doi: 10.1016/s0166-2236(96)80026-9
85. Sah, P., and Faber, E. S. (2002). Channels underlying neuronal calcium-activated potassium currents. Prog. Neurobiol. 66, 345-353. doi: 10.1016/s0301-0082(02)00004-7
86. Schmolesky, M. T., Wang, Y., Pu, M., and Leventhal, A. G. (2000). Degradation of stimulus selectivity of visual cortical cells in senescent rhesus monkeys. Nat. Neurosci. 3, 384-390. doi: 10.1038/73957
87. Sesti, F., Liu, S., and Cai, S. Q. (2010). Oxidation of potassium channels by ROS: a general mechanism of aging and neurodegeneration? Trends Cell Biol. 20, 45-51. doi: 10.1016/j.tcb.2009.09.008
88. Shao, L. R., Halvorsrud, R., Borg-Graham, L., and Storm, J. F. (1999). The role of BK-type Ca2+-dependent K+ channels in spike broadening during repetitive firing in rat hippocampal pyramidal cells. J. Physiol. 521, 135-146. doi: 10.1111/j.1469-7793.1999.00135.x
89. Sloane, J. A., Hinman, J. D., Lubonia, M., Hollander, W., and Abraham, C. R. (2003). Age-dependent myelin degeneration and proteolysis of oligodendrocyte proteins is associated with the activation of calpain-1 in the rhesus monkey. J. Neurochem. 84, 157-168. doi: 10.1046/j.1471-4159.2003.01541.x
90. Stocker, M., Krause, M., and Pedarzani, P. (1999). An apamin-sensitive Ca2+-activated K+ current in hippocampal pyramidal neurons. Proc. Natl. Acad. Sci. U S A 96, 4662-4667. doi: 10.1073/pnas.96.8.4662
91. Storm, J. F. (1990). Potassium currents in hippocampal pyramidal cells. Prog. Brain Res. 83, 161-187. doi: 10.1016/s0079-6123(08)61248-0
92. Sugiyama, I., Tanaka, K., Akita, M., Yoshida, K., Kawase, T., and Asou, H. (2002). Ultrastructural analysis of the paranodal junction of myelinated fibers in 31-month-old-rats. J. Neurosci. Res. 70, 309-317. doi: 10.1002/jnr.10386
93. Tanaka, Y., and Ando, S. (2001). Age-related changes in the subtypes of voltage-dependent calcium channels in rat brain cortical synapses. Neurosci. Res. 39, 213-220. doi: 10.1016/s0168-0102(00)00212-1
94. Thibault, O., Hadley, R., and Landfield, P. W. (2001). Elevated postsynaptic [Ca2+]i and L-type calcium channel activity in aged hippocampal neurons: relationship to impaired synaptic plasticity. J. Neurosci. 21, 9744-9756.
95. Thibault, O., and Landfield, P. W. (1996). Increase in single L-type calcium channels in hippocampal neurons during aging. Science 272, 1017-1020. doi: 10.1126/science.272.5264.1017
96. Villalobos, C., Shakkottai, V. G., Chandy, K. G., Michelhaugh, S. K., and Andrade, R. (2004). SKCa channels mediate the medium but not the slow calcium-activated afterhyperpolarization in cortical neurons. J. Neurosci. 24, 3537-3542. doi: 10.1523/jneurosci.0380-04.2004
97. Wang, M., Gamo, N. J., Yang, Y., Jin, L. E., Wang, X. J., Laubach, M., et al. (2011). Neuronal basis of age-related working memory decline. Nature 476, 210-213. doi: 10.1038/nature10243
98. West, M. J. (1993). New stereological methods for counting neurons. Neurobiol. Aging 14, 275-285. doi: 10.1016/0197-4580(93)90112-o
99. West, M. J., Coleman, P. D., Flood, D. G., and Troncoso, J. C. (1994). Differences in the pattern of hippocampal neuronal loss in normal ageing and Alzheimer's disease. Lancet 344, 769-772. doi: 10.1016/s0140-6736(94)92338-8
100. Wilson, I. A., Ikonen, S., Gallagher, M., Eichenbaum, H., and Tanila, H. (2005). Age-associated alterations of hippocampal place cells are subregion specific. J. Neurosci. 25, 6877-6886. doi: 10.1523/jneurosci.1744-05.2005
101. Wong, T. P., Campbell, P. M., Ribeiro-da-Silva, A., and Cuello, A. C. (1998). Synaptic numbers across cortical laminae and cognitive performance of the rat during ageing. Neuroscience 84, 403-412. doi: 10.1016/s0306-4522(97)00485-5
102. Wong, T. P., Marchese, G., Casu, M. A., Ribeiro-da-Silva, A., Cuello, A. C., and De Koninck, Y. (2000). Loss of presynaptic and postsynaptic structures is accompanied by compensatory increase in action potential-dependent synaptic input to layer V neocortical pyramidal neurons in aged rats. J. Neurosci. 20, 8596-8606.
103. Xi, M. C., Liu, R. H., Engelhardt, J. K., Morales, F. R., and Chase, M. H. (1999). Changes in the axonal conduction velocity of pyramidal tract neurons in the aged cat. Neuroscience 92, 219-225. doi: 10.1016/s0306-4522(98)00754-4
104. Xing, Y., Samuvel, D. J., Stevens, S. M., Dubno, J. R., Schulte, B. A., and Lang, H. (2012). Age-related changes of myelin basic protein in mouse and human auditory nerve. PLoS One 7:e34500. doi: 10.1371/journal.pone.0034500
105. Yan, J., Zhang, Y., Roder, J., and Mcdonald, R. J. (2003). Aging effects on spatial tuning of hippocampal place cells in mice. Exp. Brain Res. 150, 184-193. doi: 10.1007/s00221-003-1396-6