Glutamatergic signaling and low prodynorphin expression are associated with intact memory and reduced anxiety in rat models of healthy aging

Frontiers in Aging Neuroscience

Volumn 6, Issue MAY, 2014, Pages

  Ménard, Caroline ^a,b,c,d   Quirion, Rémi ^a,b   Bouchard, Sylvain ^d   Ferland, Guylaine ^e,f   Gaudreau, Pierrette ^c,d  

^a MCGILL UNIVERSITY   (Canada)

^b MCGILL UNIVERSITY   (Canada)

^c CENTRE HOSPITALIER DE L UNIVERSITÉ DE MONTRÉAL   (Canada)

^d UNIVERSITÉ DE MONTRÉAL   (Canada)

^e HÔPITAL DU SACRÉ COEUR DE MONTRÉAL   (Canada)

^f UNIVERSITY OF MONTREAL   (Canada)

Author keywords

Aging; Anxiety; Caloric restriction; Cognition; Glutamate receptors; Obesity

Indexed keywords

ARC PROTEIN; DYNORPHIN; GLUTAMATE RECEPTOR; METABOTROPIC RECEPTOR 5; PRODYNORPHIN; PROTEIN; PROTEIN HOMER 1A; UNCLASSIFIED DRUG;

AGE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANXIETY; ARTICLE; CALORIC RESTRICTION; COGNITIVE DEFECT; ELEVATED PLUS MAZE TEST; EXPLORATORY BEHAVIOR; FEMALE; IMMEDIATE EARLY GENE; IMMUNOHISTOCHEMISTRY; LEARNING; LOCOMOTION; LONG TERM MEMORY; LOUVAIN RAT; MALE; MEMORY; MEMORY DISORDER; MORRIS WATER MAZE TEST; NERVE CELL PLASTICITY; NONHUMAN; OPEN FIELD TEST; PROTEIN EXPRESSION; RAT; SEX DIFFERENCE; SIGNAL TRANSDUCTION; SPATIAL LEARNING; SPATIAL MEMORY; UNIVERSITY; WORKING MEMORY;

EID: 84901352751     PISSN: None     EISSN: 16634365     Source Type: Journal    
DOI: 10.3389/fnagi.2014.00081     Document Type: Article

References (94)

1. Adams, M. M., Shi, L., Linville, M. C., Forbes, M. E., Long, A. B., Bennett, C., et al. (2008). Caloric restriction and age affect synaptic proteins in hippocampal CA3 and spatial learning ability. Exp. Neurol. 211, 141-149. doi: 10.1016/j.expneurol.2008.01.016
2. Alberini, C. M. (2009). Transcription factors in long-term memory and synaptic plasticity. Physiol. Rev. 89, 121-145. doi: 10.1152/physrev.00017.2008
3. Alliot, J., Boghossian, S., Jourdan, D., Veyrat-Durebex, C., Pickering, G., Meynial-Denis, D., et al. (2002). The LOU/c/jall rat as an animal model of healthy aging? J. Gerontol. A Biol. Sci. Med. Sci. 57, B312-B320. doi: 10.1093/gerona/57.8.B312
4. Balschun, D., Manahan-Vaughan, D., Wagner, T., Behnisch, T., Reymann, K. G., and Wetzel, W. (1999). A specific role for group I mGluRs in hippocampal LTP and hippocampus-dependent spatial learning. Learn. Mem. 6, 138-152. doi: 10.1101/lm.6.2.138
5. Barker, G. R., Bashir, Z. I., Brown, M. W., and Warburton, E. C. (2006). A temporally distinct role for group I and group II metabotropic glutamate receptors in object recognition memory. Learn. Mem. 13, 178-186. doi: 10.1101/lm.77806
6. Baudry, M., Bi, X., Gall, C., and Lynch, G. (2011). The biochemistry of memory: the 26year journey of a 'new and specific hypothesis.' Neurobiol. Learn. Mem. 95, 125-133. doi: 10.1016/j.nlm.2010.11.015
7. Bedard, K., Bedard, J., Rocheleau, G., Ferland, G., and Gaudreau, P. (2013). Aging and diets regulate the rat anterior pituitary and hypothalamic transcriptome. Neuroendocrinology 97, 146-159. doi: 10.1159/000338411
8. Bedard, K., Robinette, K., Ferland, G., and Gaudreau, P. (2010). Effects of long-term dietary interventions on pituitary growth hormone-releasing hormone receptor in aging rats and potential mechanisms of action. Mech. Ageing Dev. 131, 169-178. doi: 10.1016/j.mad.2010.01.003
9. Beique, J. C., Na, Y., Kuhl, D., Worley, P. F., and Huganir, R. L. (2011). Arc-dependent synapse-specific homeostatic plasticity. Proc. Natl. Acad. Sci. U.S.A. 108, 816-821. doi: 10.1073/pnas.1017914108
10. Benoit, C. E., Rowe, W. B., Menard, C., Sarret, P., and Quirion, R. (2011). Genomic and proteomic strategies to identify novel targets potentially involved in learning and memory. Trends Pharmacol. Sci. 32, 43-52. doi: 10.1016/j.tips.2010.10.002
11. Bilkei-Gorzo, A., Erk, S., Schurmann, B., Mauer, D., Michel, K., Boecker, H., et al. (2012). Dynorphins regulate fear memory: from mice to men. J. Neurosci. 32, 9335-9343. doi: 10.1523/JNEUROSCI.1034-12.2012
12. Bodnoff, S. R., Humphreys, A. G., Lehman, J. C., Diamond, D. M., Rose, G. M., and Meaney, M. J. (1995). Enduring effects of chronic corticosterone treatment on spatial learning, synaptic plasticity, and hippocampal neuropathology in young and mid-aged rats. J. Neurosci. 15, 61-69.
13. Bradbury, M. J., Campbell, U., Giracello, D., Chapman, D., King, C., Tehrani, L., et al. (2005). Metabotropic glutamate receptor mGlu5 is a mediator of appetite and energy balance in rats and mice. J. Pharmacol. Exp. Ther. 313, 395-402. doi: 10.1124/jpet.104.076406
14. Bramham, C. R., Worley, P. F., Moore, M. J., and Guzowski, J. F. (2008). The immediate early gene arc/arg3.1: regulation, mechanisms, and function. J. Neurosci. 28, 11760-11767. doi: 10.1523/JNEUROSCI.3864-08.2008
15. Brim, B. L., Haskell, R., Awedikian, R., Ellinwood, N. M., Jin, L., Kumar, A., et al. (2012). Memory in aged mice is rescued by enhanced expression of the GluN2B subunit of the NMDA receptor. Behav. Brain Res. 238C, 211-226. doi: 10.1016/j.bbr.2012.10.026
16. Bunce, D., Batterham, P. J., Mackinnon, A. J., and Christensen, H. (2012). Depression, anxiety and cognition in community-dwelling adults aged 70 years and over. J. Psychiatr. Res. 46, 1662-1666. doi: 10.1016/j.jpsychires.2012.08.023
17. Burke, S. N., Ryan, L., and Barnes, C. A. (2012). Characterizing cognitive aging of recognition memory and related processes in animal models and in humans. Front. Aging Neurosci. 4:15. doi: 10.3389/fnagi.2012.00015
18. Burke, S. N., Wallace, J. L., Hartzell, A. L., Nematollahi, S., Plange, K., and Barnes, C. A. (2011). Age-associated deficits in pattern separation functions of the perirhinal cortex: a cross-species consensus. Behav. Neurosci. 125, 836-847. doi: 10.1037/a0026238
19. Carey, A. N., Lyons, A. M., Shay, C. F., Dunton, O., and McLaughlin, J. P. (2009). Endogenous kappa opioid activation mediates stress-induced deficits in learning and memory. J. Neurosci. 29, 4293-4300. doi: 10.1523/JNEUROSCI.6146-08.2009
20. Carter, C. S., Leeuwenburgh, C., Daniels, M., and Foster, T. C. (2009). Influence of calorie restriction on measures of age-related cognitive decline: role of increased physical activity. J. Gerontol. A Biol. Sci. Med. Sci. 64, 850-859. doi: 10.1093/gerona/glp060
21. Christoffersen, G. R., Simonyi, A., Schachtman, T. R., Clausen, B., Clement, D., Bjerre, V. K., et al. (2008). MGlu5 antagonism impairs exploration and memory of spatial and non-spatial stimuli in rats. Behav. Brain Res. 191, 235-245. doi: 10.1016/j.bbr.2008.03.032
22. Czerniawski, J., Ree, F., Chia, C., Ramamoorthi, K., Kumata, Y., and Otto, T. A. (2011). The importance of having Arc: expression of the immediate-early gene Arc is required for hippocampus-dependent fear conditioning and blocked by NMDA receptor antagonism. J. Neurosci. 31, 11200-11207. doi: 10.1523/JNEUROSCI.2211-11.2011
23. Fadel, J. R., Jolivalt, C. G., and Reagan, L. P. (2013). Food for thought: the role of appetitive peptides in age-related cognitive decline. Ageing Res. Rev. 12, 764-776. doi: 10.1016/j.arr.2013.01.009
24. Fontan-Lozano, A., Saez-Cassanelli, J. L., Inda, M. C., De Los Santos-Arteaga, M., Sierra-Dominguez, S. A., Lopez-Lluch, G., et al. (2007). Caloric restriction increases learning consolidation and facilitates synaptic plasticity through mechanisms dependent on NR2B subunits of the NMDA receptor. J. Neurosci. 27, 10185-10195. doi: 10.1523/JNEUROSCI.2757-07.2007
25. Frankland, P. W., and Bontempi, B. (2005). The organization of recent and remote memories. Nat. Rev. Neurosci. 6, 119-130. doi: 10.1038/nrn1607
26. Geiger, J. R., Melcher, T., Koh, D. S., Sakmann, B., Seeburg, P. H., Jonas, P., et al. (1995). Relative abundance of subunit mRNAs determines gating and Ca2+ permeability of AMPA receptors in principal neurons and interneurons in rat CNS. Neuron 15, 193-204. doi: 10.1016/0896-6273(95)90076-4
27. Guzowski, J. F., Setlow, B., Wagner, E. K., and McGaugh, J. L. (2001). Experience-dependent gene expression in the rat hippocampus after spatial learning: a comparison of the immediate-early genes Arc, c-fos, and zif268. J. Neurosci. 21, 5089-5098.
28. Harrison, F. E., Hosseini, A. H., and McDonald, M. P. (2009). Endogenous anxiety and stress responses in water maze and Barnes maze spatial memory tasks. Behav. Brain Res. 198, 247-251. doi: 10.1016/j.bbr.2008.10.015
29. Holloway, C. M., and McIntyre, C. K. (2011). Post-training disruption of Arc protein expression in the anterior cingulate cortex impairs long-term memory for inhibitory avoidance training. Neurobiol. Learn. Mem. 95, 425-432. doi: 10.1016/j.nlm.2011.02.002
30. Huganir, R. L., and Nicoll, R. A. (2013). AMPARs and synaptic plasticity: the last 25 years. Neuron 80, 704-717. doi: 10.1016/j.neuron.2013.10.025
31. Inoue, N., Nakao, H., Migishima, R., Hino, T., Matsui, M., Hayashi, F., et al. (2009). Requirement of the immediate early gene vesl-1S/homer-1a for fear memory formation. Mol. Brain 2, 7. doi: 10.1186/1756-6606-2-7
32. Inoue, Y., Udo, H., Inokuchi, K., and Sugiyama, H. (2007). Homer1a regulates the activity-induced remodeling of synaptic structures in cultured hippocampal neurons. Neuroscience 150, 841-852. doi: 10.1016/j.neuroscience.2007.09.081
33. Inta, D., Vogt, M. A., Luoni, A., Filipovic, D., Lima-Ojeda, J. M., Pfeiffer, N., et al. (2013). Significant increase in anxiety during aging in mGlu5 receptor knockout mice. Behav. Brain Res. 241, 27-31. doi: 10.1016/j.bbr.2012.11.042
34. Kaja, S., Sumien, N., Borden, P. K., Khullar, N., Iqbal, M., Collins, J. L., et al. (2013). Homer-1a immediate early gene expression correlates with better cognitive performance in aging. Age 35, 1799-1808. doi: 10.1007/s11357-012-9479-6
35. Kammermeier, P. J., and Worley, P. F. (2007). Homer 1a uncouples metabotropic glutamate receptor 5 from postsynaptic effectors. Proc. Natl. Acad. Sci. U.S.A. 104, 6055-6060. doi: 10.1073/pnas.0608991104
36. Kesner, R. P. (2007). Behavioral functions of the CA3 subregion of the hippocampus. Learn. Mem. 14, 771-781. doi: 10.1101/lm.688207
37. Kim, E. M., Welch, C. C., Grace, M. K., Billington, C. J., and Levine, A. S. (1996). Chronic food restriction and acute food deprivation decrease mRNA levels of opioid peptides in arcuate nucleus. Am. J. Physiol. 270, R1019-R1024.
38. Klugmann, M., Symes, C. W., Leichtlein, C. B., Klaussner, B. K., Dunning, J., Fong, D., et al. (2005). AAV-mediated hippocampal expression of short and long Homer 1 proteins differentially affect cognition and seizure activity in adult rats. Mol. Cell. Neurosci. 28, 347-360. doi: 10.1016/j.mcn.2004.10.002
39. Kollen, M., Stephan, A., Faivre-Bauman, A., Loudes, C., Sinet, P. M., Alliot, J., et al. (2010). Preserved memory capacities in aged Lou/C/Jall rats. Neurobiol. Aging 31, 129-142. doi: 10.1016/j.neurobiolaging.2008.03.010
40. Kotz, C. M., Weldon, D., Billington, C. J., and Levine, A. S. (2004). Age-related changes in brain proDynorphin gene expression in the rat. Neurobiol. Aging 25, 1343-1347. doi: 10.1016/j.neurobiolaging.2004.02.025
41. Landfield, P. W., Baskin, R. K., and Pitler, T. A. (1981). Brain aging correlates: retardation by hormonal-pharmacological treatments. Science 214, 581-584. doi: 10.1126/science.6270791
42. Lee, H. K., Min, S. S., Gallagher, M., and Kirkwood, A. (2005). NMDA receptor-independent long-term depression correlates with successful aging in rats. Nat. Neurosci. 8, 1657-1659. doi: 10.1038/nn1586
43. Levay, E. A., Tammer, A. H., Penman, J., Kent, S., and Paolini, A. G. (2010). Calorie restriction at increasing levels leads to augmented concentrations of corticosterone and decreasing concentrations of testosterone in rats. Nutr. Res. 30, 366-373. doi: 10.1016/j.nutres.2010.05.001
44. Lu, Y. M., Jia, Z., Janus, C., Henderson, J. T., Gerlai, R., Wojtowicz, J. M., et al. (1997). Mice lacking metabotropic glutamate receptor 5 show impaired learning and reduced CA1 long-term potentiation (LTP) but normal CA3 LTP. J. Neurosci. 17, 5196-5205.
45. Lupien, S. J., Fiocco, A., Wan, N., Maheu, F., Lord, C., Schramek, T., et al. (2005). Stress hormones and human memory function across the lifespan. Psychoneuroendocrinology 30, 225-242. doi: 10.1016/j.psyneuen.2004.08.003
46. Lupien, S. J., McEwen, B. S., Gunnar, M. R., and Heim, C. (2009). Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat. Rev. Neurosci. 10, 434-445. doi: 10.1038/nrn2639
47. Marissal-Arvy, N., Gaumont, A., Langlois, A., Dabertrand, F., Bouchecareilh, M., Tridon, C., et al. (2007). Strain differences in hypothalamic pituitary adrenocortical axis function and adipogenic effects of corticosterone in rats. J. Endocrinol. 195, 473-484. doi: 10.1677/JOE-07-0077
48. Markowska, A. L., Mooney, M., and Sonntag, W. E. (1998). Insulin-like growth factor-1 ameliorates age-related behavioral deficits. Neuroscience 87, 559-569. doi: 10.1016/S0306-4522(98)00143-2
49. Markowska, A. L., and Savonenko, A. (2002). Retardation of cognitive aging by life-long diet restriction: implications for genetic variance. Neurobiol. Aging 23, 75-86. doi: 10.1016/S0197-4580(01)00249-4
50. Mathus-Vliegen, E. M. (2012). Obesity and the elderly. J. Clin. Gastroenterol. 46, 533-544. doi: 10.1097/MCG.0b013e31825692ce
51. Menard, C., Chartier, E., Patenaude, C., Robinson, P., Cyr, M., Baudry, M., et al. (2007). Calcium-independent phospholipase A(2) influences AMPA-mediated toxicity of hippocampal slices by regulating the GluR1 subunit in synaptic membranes. Hippocampus 17, 1109-1120. doi: 10.1002/hipo.20343
52. Menard, C., Herzog, H., Schwarzer, C., and Quirion, R. (2014). Possible role of dynorphins in Alzheimer's disease and age-related cognitive deficits. Neurodegener. Dis. 13, 82-85. doi: 10.1159/000353848
53. Menard, C., and Quirion, R. (2012a). Group 1 metabotropic glutamate receptor function and its regulation of learning and memory in the aging brain. Front. Pharmacol. 3:182. doi: 10.3389/fphar.2012.00182
54. Menard, C., and Quirion, R. (2012b). Successful cognitive aging in rats: a role for mGluR5 glutamate receptors, homer 1 proteins and downstream signaling pathways. PLoS ONE 7:e28666. doi: 10.1371/journal.pone.0028666
55. Menard, C., Tse, Y. C., Cavanagh, C., Chabot, J. G., Herzog, H., Schwarzer, C., et al. (2013). Knockdown of prodynorphin gene prevents cognitive decline, reduces anxiety, and rescues loss of group 1 metabotropic glutamate receptor function in aging. J. Neurosci. 33, 12792-12804. doi: 10.1523/JNEUROSCI.0290-13.2013
56. Menard, C., Valastro, B., Martel, M. A., Martinoli, M. G., and Massicotte, G. (2004). Strain-related variations of AMPA receptor modulation by calcium-dependent mechanisms in the hippocampus: contribution of lipoxygenase metabolites of arachidonic acid. Brain Res. 1010, 134-143. doi: 10.1016/j.brainres.2004.03.012
57. Moura, P. J., Meirelles, S. T., and Xavier, G. F. (2010). Long-term social recognition memory in adult male rats: factor analysis of the social and non-social behaviors. Braz. J. Med. Biol. Res. 43, 663-676. doi: 10.1590/S0100-879X2010007500047
58. Moyse, E., Bedard, K., Segura, S., Mahaut, S., Tardivel, C., Ferland, G., et al. (2012). Effects of aging and caloric restriction on brainstem satiety center signals in rats. Mech. Ageing Dev. 133, 83-91. doi: 10.1016/j.mad.2012.01.004
59. Newmark, R. E., Schon, K., Ross, R. S., and Stern, C. E. (2013). Contributions of the hippocampal subfields and entorhinal cortex to disambiguation during working memory. Hippocampus 23, 467-475. doi: 10.1002/hipo.22106
60. Nguyen, X. V., Masse, J., Kumar, A., Vijitruth, R., Kulik, C., Liu, M., et al. (2005). Prodynorphin knockout mice demonstrate diminished age-associated impairment in spatial water maze performance. Behav. Brain Res. 161, 254-262. doi: 10.1016/j.bbr.2005.02.010
61. Nikbakht, N., Zarei, B., Shirani, E., Moshtaghian, J., Esmaeili, A., and Habibian, S. (2012). Experience-dependent expression of rat hippocampal Arc and Homer 1a after spatial learning on 8-arm and 12-arm radial mazes. Neuroscience 218, 49-55. doi: 10.1016/j.neuroscience.2012.05.025
62. O'Donovan, A., Slavich, G. M., Epel, E. S., and Neylan, T. C. (2013). Exaggerated neurobiological sensitivity to threat as a mechanism linking anxiety with increased risk for diseases of aging. Neurosci. Biobehav. Rev. 37, 96-108. doi: 10.1016/j.neubiorev.2012.10.013
63. Paban, V., Billard, J. M., Bouet, V., Freret, T., Boulouard, M., Chambon, C., et al. (2012). Genomic transcriptional profiling in LOU/C/Jall rats identifies genes for successful aging. Brain Struct. Funct. 218, 1501-1512. doi: 10.1007/s00429-012-0472-8
64. Penner, M. R., Roth, T. L., Chawla, M. K., Hoang, L. T., Roth, E. D., Lubin, F. D., et al. (2011). Age-related changes in Arc transcription and DNA methylation within the hippocampus. Neurobiol. Aging 32, 2198-2210. doi: 10.1016/j.neurobiolaging.2010.01.009
65. Qiu, G., Spangler, E. L., Wan, R., Miller, M., Mattson, M. P., So, K. F., et al. (2012). Neuroprotection provided by dietary restriction in rats is further enhanced by reducing glucocortocoids. Neurobiol. Aging 33, 2398-2410. doi: 10.1016/j.neurobiolaging.2011.11.025
66. Rossi-Arnaud, C., and Ammassari-Teule, M. (1998). What do comparative studies of inbred mice add to current investigations on the neural basis of spatial behaviors? Exp. Brain Res. 123, 36-44. doi: 10.1007/s002210050542
67. Rowe, W. B., Blalock, E. M., Chen, K. C., Kadish, I., Wang, D., Barrett, J. E., et al. (2007). Hippocampal expression analyses reveal selective association of immediate-early, neuroenergetic, and myelinogenic pathways with cognitive impairment in aged rats. J. Neurosci. 27, 3098-3110. doi: 10.1523/JNEUROSCI.4163-06.2007
68. Russo, S. J., Murrough, J. W., Han, M. H., Charney, D. S., and Nestler, E. J. (2012). Neurobiology of resilience. Nat. Neurosci. 15, 1475-1484. doi: 10.1038/nn.3234
69. Sandi, C. (2011). Glucocorticoids act on glutamatergic pathways to affect memory processes. Trends Neurosci. 34, 165-176. doi: 10.1016/j.tins.2011.01.006
70. Schwarzer, C. (2009). 30 years of dynorphins-new insights on their functions in neuropsychiatric diseases. Pharmacol. Ther. 123, 353-370. doi: 10.1016/j.pharmthera.2009.05.006
71. Shepherd, J. D., and Bear, M. F. (2011). New views of Arc, a master regulator of synaptic plasticity. Nat. Neurosci. 14, 279-284. doi: 10.1038/nn.2708
72. Shukitt-Hale, B., Casadesus, G., Cantuti-Castelvetri, I., and Joseph, J. A. (2001). Effect of age on object exploration, habituation, and response to spatial and nonspatial change. Behav. Neurosci. 115, 1059-1064. doi: 10.1037//0735-7044.115.5.1059
73. Simmons, M. L., Terman, G. W., Drake, C. T., and Chavkin, C. (1994). Inhibition of glutamate release by presynaptic kappa 1-opioid receptors in the guinea pig dentate gyrus. J. Neurophysiol. 72, 1697-1705.
74. Sommer, B., Kohler, M., Sprengel, R., and Seeburg, P. H. (1991). RNA editing in brain controls a determinant of ion flow in glutamate-gated channels. Cell 67, 11-19. doi: 10.1016/0092-8674(91)90568-J
75. Stranahan, A. M., and Mattson, M. P. (2011). Bidirectional metabolic regulation of neurocognitive function. Neurobiol. Learn. Mem. 96, 507-516. doi: 10.1016/j.nlm.2011.01.004
76. Traissard, N., Herbeaux, K., Cosquer, B., Jeltsch, H., Ferry, B., Galani, R., et al. (2007). Combined damage to entorhinal cortex and cholinergic basal forebrain neurons, two early neurodegenerative features accompanying Alzheimer's disease: effects on locomotor activity and memory functions in rats. Neuropsychopharmacology 32, 851-871. doi: 10.1038/sj.npp.1301116
77. Tronson, N. C., Guzman, Y. F., Guedea, A. L., Huh, K. H., Gao, C., Schwarz, M. K., et al. (2010). Metabotropic glutamate receptor 5/Homer interactions underlie stress effects on fear. Biol. Psychiatry 68, 1007-1015. doi: 10.1016/j.biopsych.2010.09.004
78. Umegaki, H., Hayashi, T., Nomura, H., Yanagawa, M., Nonogaki, Z., Nakshima, H., et al. (2013). Cognitive dysfunction: an emerging concept of a new diabetic complication in the elderly. Geriatr. Gerontol. Int. 13, 28-34. doi: 10.1111/j.1447-0594.2012.00922.x
79. Upchurch, M., and Wehner, J. M. (1988). DBA/2Ibg mice are incapable of cholinergically-based learning in the Morris water task. Pharmacol. Biochem. Behav. 29, 325-329. doi: 10.1016/0091-3057(88)90164-5
80. Upchurch, M., and Wehner, J. M. (1989). Inheritance of spatial learning ability in inbred mice: a classical genetic analysis. Behav. Neurosci. 103, 1251-1258. doi: 10.1037/0735-7044.103.6.1251
81. Vahia, I. V., Chattillion, E., Kavirajan, H., and Depp, C. A. (2011). Psychological protective factors across the lifespan: implications for psychiatry. Psychiatr. Clin. North Am. 34, 231-248. doi: 10.1016/j.psc.2010.11.011
82. Veyrat-Durebex, C., Alliot, J., and Gaudreau, P. (2005). Regulation of the pituitary growth hormone-releasing hormone receptor in ageing male and female LOU rats: new insights into healthy ageing. J. Neuroendocrinol. 17, 691-700. doi: 10.1111/j.1365-2826.2005.01343.x
83. Veyrat-Durebex, C., Montet, X., Vinciguerra, M., Gjinovci, A., Meda, P., Foti, M., et al. (2009). The Lou/C rat: a model of spontaneous food restriction associated with improved insulin sensitivity and decreased lipid storage in adipose tissue. Am. J. Physiol. Endocrinol. Metab. 296, E1120-E1132. doi: 10.1152/ajpendo.90592.2008
84. Veyrat-Durebex, C., Poher, A. L., Caillon, A., Somm, E., Vallet, P., Charnay, Y., et al. (2013). Improved leptin sensitivity as a potential candidate responsible for the spontaneous food restriction of the lou/c rat. PLoS ONE 8:e73452. doi: 10.1371/journal.pone.0073452
85. Wagner, J. J., Terman, G. W., and Chavkin, C. (1993). Endogenous dynorphins inhibit excitatory neurotransmission and block LTP induction in the hippocampus. Nature 363, 451-454. doi: 10.1038/363451a0
86. Wagner, K. V., Hartmann, J., Mangold, K., Wang, X. D., Labermaier, C., Liebl, C., et al. (2013). Homer1 mediates acute stress-induced cognitive deficits in the dorsal hippocampus. J. Neurosci. 33, 3857-3864. doi: 10.1523/JNEUROSCI.4333-12.2013
87. Whittington, R. A., Bretteville, A., Virag, L., Emala, C. W., Maurin, T. O., Marcouiller, F., et al. (2013). Anesthesia-induced hypothermia mediates decreased ARC gene and protein expression through ERK/MAPK inactivation. Sci. Rep. 3, 1388. doi: 10.1038/srep01388
88. Williamson, R., McNeilly, A., and Sutherland, C. (2012). Insulin resistance in the brain: an old-age or new-age problem? Biochem. Pharmacol. 84, 737-745. doi: 10.1016/j.bcp.2012.05.007
89. Wittmann, W., Schunk, E., Rosskothen, I., Gaburro, S., Singewald, N., Herzog, H., et al. (2009). Prodynorphin-derived peptides are critical modulators of anxiety and regulate neurochemistry and corticosterone. Neuropsychopharmacology 34, 775-785. doi: 10.1038/npp.2008.142
90. Xu, J., Zhu, Y., Contractor, A., and Heinemann, S. F. (2009). mGluR5 has a critical role in inhibitory learning. J. Neurosci. 29, 3676-3684. doi: 10.1523/JNEUROSCI.5716-08.2009
91. Yamamoto, Y., Tanahashi, T., Kawai, T., Chikahisa, S., Katsuura, S., Nishida, K., et al. (2009). Changes in behavior and gene expression induced by caloric restriction in C57BL/6 mice. Physiol. Genomics 39, 227-235. doi: 10.1152/physiolgenomics.00082.2009
92. Yang, S., Megill, A., Ardiles, A. O., Ransom, S., Tran, T., Koh, M. T., et al. (2013). Integrity of mGluR-LTD in the Associative/Commissural Inputs to CA3 Correlates with Successful Aging in Rats. J. Neurosci. 33, 12670-12678. doi: 10.1523/JNEUROSCI.1086-13.2013
93. Zhao, X., Rosenke, R., Kronemann, D., Brim, B., Das, S. R., Dunah, A. W., et al. (2009). The effects of aging on N-methyl-D-aspartate receptor subunits in the synaptic membrane and relationships to long-term spatial memory. Neuroscience 162, 933-945. doi: 10.1016/j.neuroscience.2009.05.018
94. Zyzak, D. R., Otto, T., Eichenbaum, H., and Gallagher, M. (1995). Cognitive decline associated with normal aging in rats: a neuropsychological approach. Learn. Mem. 2, 1-16. doi: 10.1101/lm.2.1.1