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Pattern Separation: A Key Processing Deficit Associated with Aging?

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The Neurobiological Basis of Memory

Abstract

Age-related memory impairment has been well documented in older adults and may serve as an early indicator of mild cognitive impairment or Alzheimer’s disease in some individuals. The work of Dr. Raymond Kesner has shown that pattern separation is a critical mechanism, supported by the dentate gyrus and CA3 hippocampal subregions, for reducing potential interference among similar memory representations to enhance memory accuracy. A growing literature indicates that pattern separation becomes less efficient with normal aging as a result of age-related changes in the hippocampus and its perforant path input. Researchers have hypothesized that decreased pattern separation efficiency may be a key processing deficit that could contribute to memory impairment associated with aging. In this chapter, we will review studies that have examined age-related changes in pattern separation in humans and rodents. In addition, we will discuss the potential basic science, translational, and clinical implications from these studies to illustrate the need to further examine the relationship between the brain changes associated with aging and pattern separation. The innovative behavioral studies to examine pattern separation conducted in the laboratory of Dr. Raymond Kesner have contributed greatly to our understanding of this mnemonic process and have set the foundation for the behavioral investigation of age-related changes in pattern separation.

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References

  • Aimone, J. B., Deng, W., & Gage, F. H. (2010). Adult neurogenesis: integrating theories and separating functions. Trends in Cognitive Sciences, 14(7), 325–337. doi:10.1016/j.tics.2010.04.003.

    Article  PubMed Central  PubMed  Google Scholar 

  • Aimone, J. B., Deng, W., & Gage, F. H. (2011). Resolving new memories: A critical look at the dentate gyrus, adult neurogenesis, and pattern separation. Neuron, 70(4), 589–596. doi:10.1016/j.neuron.2011.05.010.

    Article  PubMed Central  PubMed  Google Scholar 

  • Allen, J. S., Bruss, J., Brown, C. K., & Damasio, H. (2005). Normal neuroanatomical variation due to age: The major lobes and a parcellation of the temporal region. Neurobiology of Aging, 26(9), 1245–1260 (discussion 1279–1282). doi:10.1016/j.neurobiolaging.2005.05.023.

    Article  PubMed  Google Scholar 

  • Ally, B. A., Hussey, E. P., Ko, P. C., & Molitor, R. J. (2013). Pattern separation and pattern completion in Alzheimer’s disease: Evidence of rapid forgetting in amnestic mild cognitive impairment. Hippocampus, 23(12), 1246–1258. doi:10.1002/hipo.22162.

    Article  PubMed Central  PubMed  Google Scholar 

  • Alzheimer’s Association. (2012). 2012 Alzheimer’s disease facts and figures. Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, 8(2), 131–168. doi:10.1016/j.jalz.2012.02.001.

    Article  Google Scholar 

  • Apostolova, L. G., Hwang, K. S., Andrawis, J. P., Green, A. E., Babakchanian, S., Morra, J. H., Cummings, J. L., et al. (2010). 3D PIB and CSF biomarker associations with hippocampal atrophy in ADNI subjects. Neurobiology of Aging, 31(8), 1284–1303. doi:10.1016/j.neurobiolaging.2010.05.003.

    Article  PubMed Central  PubMed  Google Scholar 

  • Bakker, A., Kirwan, C. B., Miller, M., & Stark, C. E. L. (2008). Pattern separation in the human hippocampal CA3 and dentate gyrus. Science (New York, N.Y.), 319(5870), 1640–1642. doi:10.1126/science.1152882.

    Article  Google Scholar 

  • Barense, M. D., Henson, R. N. A., Lee, A. C. H., & Graham, K. S. (2010). Medial temporal lobe activity during complex discrimination of faces, objects, and scenes: Effects of viewpoint. Hippocampus, 20(3), 389–401. doi:10.1002/hipo.20641.

    PubMed Central  PubMed  Google Scholar 

  • Barnes, C. A. (1994). Normal aging: Regionally specific changes in hippocampal synaptic transmission. Trends in Neurosciences, 17(1), 13–18.

    Article  PubMed  Google Scholar 

  • Barnes, D. C., Hofacer, R. D., Zaman, A. R., Rennaker, R. L., & Wilson, D. A. (2008). Olfactory perceptual stability and discrimination. Nature Neuroscience, 11(12), 1378–1380. doi:10.1038/nn.2217.

    Article  PubMed Central  PubMed  Google Scholar 

  • Bartko, S. J., Winters, B. D., Cowell, R. A., Saksida, L. M., & Bussey, T. J. (2007a). Perceptual functions of perirhinal cortex in rats: zero-delay object recognition and simultaneous oddity discriminations. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 27(10), 2548–2559. doi:10.1523/JNEUROSCI.5171-06.2007.

    Article  Google Scholar 

  • Bartko, S. J., Winters, B. D., Cowell, R. A., Saksida, L. M., & Bussey, T. J. (2007b). Perirhinal cortex resolves feature ambiguity in configural object recognition and perceptual oddity tasks. Learning & Memory (Cold Spring Harbor, N.Y.), 14(12), 821–832. doi:10.1101/lm.749207.

    Article  Google Scholar 

  • Bondi, M. W., Salmon, D. P., Galasko, D., Thomas, R. G., & Thal, L. J. (1999). Neuropsychological function and apolipoprotein E genotype in the preclinical detection of Alzheimer’s disease. Psychology and Aging, 14(2), 295–303.

    Article  PubMed  Google Scholar 

  • Braak, H., & Braak, E. (1996). Development of Alzheimer-related neurofibrillary changes in the neocortex inversely recapitulates cortical myelogenesis. Acta Neuropathologica, 92(2), 197–201.

    Article  PubMed  Google Scholar 

  • Brickman, A. M., Stern, Y., & Small, S. A. (2011). Hippocampal subregions differentially associate with standardized memory tests. Hippocampus, 21(9), 923–928. doi:10.1002/hipo.20840.

    PubMed Central  PubMed  Google Scholar 

  • Burke, S. N., & Barnes, C. A. (2006). Neural plasticity in the ageing brain. Nature Reviews Neuroscience, 7(1), 30–40. doi:10.1038/nrn1809.

    Article  PubMed  Google Scholar 

  • Burke, S. N., Wallace, J. L., Nematollahi, S., Uprety, A. R., & Barnes, C. A. (2010). Pattern separation deficits may contribute to age-associated recognition impairments. Behavioral Neuroscience, 124(5), 559–573. doi:10.1037/a0020893.

    Article  PubMed Central  PubMed  Google Scholar 

  • Burke, S. N., Wallace, J. L., Hartzell, A. L., Nematollahi, S., Plange, K., & Barnes, C. A. (2011). Age-associated deficits in pattern separation functions of the perirhinal cortex: A cross-species consensus. Behavioral Neuroscience, 125(6), 836–847. doi:10.1037/a0026238.

    Article  PubMed Central  PubMed  Google Scholar 

  • Burke, S. N., Ryan, L., & Barnes, C. A. (2012). Characterizing cognitive aging of recognition memory and related processes in animal models and in humans. Frontiers in Aging Neuroscience, 4, 15. doi:10.3389/fnagi.2012.00015.

    Article  PubMed Central  PubMed  Google Scholar 

  • Bussey, T. J., Saksida, L. M., & Murray, E. A. (2003). Impairments in visual discrimination after perirhinal cortex lesions: Testing “declarative” vs. “perceptual-mnemonic” views of perirhinal cortex function. The European Journal of Neuroscience, 17(3), 649–660.

    Article  PubMed  Google Scholar 

  • Bussey, T. J., Saksida, L. M., & Murray, E. A. (2006). Perirhinal cortex and feature-ambiguous discriminations. Learning & Memory (Cold Spring Harbor, N.Y.), 13(2), 103–105 (author reply 106–107). doi:10.1101/lm.163606.

    Article  Google Scholar 

  • Butterly, D. A., Petroccione, M. A., & Smith, D. M. (2012). Hippocampal context processing is critical for interference free recall of odor memories in rats. Hippocampus, 22(4), 906–913. doi:10.1002/hipo.20953.

    Article  PubMed Central  PubMed  Google Scholar 

  • Carr, V. A., Rissman, J., & Wagner, A. D. (2010). Imaging the human medial temporal lobe with high-resolution fMRI. Neuron, 65(3), 298–308. doi:10.1016/j.neuron.2009.12.022.

    Article  PubMed Central  PubMed  Google Scholar 

  • Clelland, C. D., Choi, M., Romberg, C., Clemenson, G. D., Jr, Fragniere, A., Tyers, P., Jessberger, S., et al. (2009). A functional role for adult hippocampal neurogenesis in spatial pattern separation. Science (New York, N.Y.), 325(5937), 210–213. doi:10.1126/science.1173215.

    Article  Google Scholar 

  • Creer, D. J., Romberg, C., Saksida, L. M., van Praag, H., & Bussey, T. J. (2010). Running enhances spatial pattern separation in mice. Proceedings of the National Academy of Sciences of the United States of America, 107(5), 2367–2372. doi:10.1073/pnas.0911725107.

    Article  PubMed Central  PubMed  Google Scholar 

  • Deng, W., Aimone, J. B., & Gage, F. H. (2010). New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? Nature Reviews Neuroscience, 11(5), 339–350. doi:10.1038/nrn2822.

    Article  PubMed Central  PubMed  Google Scholar 

  • Driscoll, I., & Sutherland, R. J. (2005). The aging hippocampus: navigating between rat and human experiments. Reviews in the Neurosciences, 16(2), 87–121.

    Article  PubMed  Google Scholar 

  • Driscoll, I., Howard, S. R., Stone, J. C., Monfils, M. H., Tomanek, B., Brooks, W. M., & Sutherland, R. J. (2006). The aging hippocampus: A multi-level analysis in the rat. Neuroscience, 139(4), 1173–1185. doi:10.1016/j.neuroscience.2006.01.040.

    Article  PubMed  Google Scholar 

  • Driscoll, I., Davatzikos, C., An, Y., Wu, X., Shen, D., Kraut, M., & Resnick, S. M. (2009). Longitudinal pattern of regional brain volume change differentiates normal aging from MCI. Neurology, 72(22), 1906–1913. doi:10.1212/WNL.0b013e3181a82634.

    Article  PubMed Central  PubMed  Google Scholar 

  • Duff, M. C., Warren, D. E., Gupta, R., Vidal, J. P. B., Tranel, D., & Cohen, N. J. (2012). Teasing apart tangrams: Testing hippocampal pattern separation with a collaborative referencing paradigm. Hippocampus, 22(5), 1087–1091. doi:10.1002/hipo.20967.

    Article  PubMed Central  PubMed  Google Scholar 

  • Gallagher, M., Bakker, A., Yassa, M. A., & Stark, C. E. L. (2010). Bridging neurocognitive aging and disease modification: Targeting functional mechanisms of memory impairment. Current Alzheimer Research, 7(3), 197–199.

    Article  PubMed Central  PubMed  Google Scholar 

  • Geinisman, Y., deToledo-Morrell, L., Morrell, F., Persina, I. S., & Rossi, M. (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(4), 437–444. doi:10.1002/hipo.450020411.

    Article  PubMed  Google Scholar 

  • Gilbert, P. E., & Kesner, R. P. (2002). The amygdala but not the hippocampus is involved in pattern separation based on reward value. Neurobiology of Learning and Memory, 77(3), 338–353. doi:10.1006/nlme.2001.4033.

    Article  PubMed  Google Scholar 

  • Gilbert, P. E., & Kesner, R. P. (2003). Recognition memory for complex visual discriminations is influenced by stimulus interference in rodents with perirhinal cortex damage. Learning and Memory (Cold Spring Harbor, N.Y.), 10(6), 525–530. doi:10.1101/lm.64503.

    Article  Google Scholar 

  • Gilbert, P. E., & Kesner, R. P. (2006). The role of the dorsal CA3 hippocampal subregion in spatial working memory and pattern separation. Behavioural Brain Research, 169(1), 142–149. doi:10.1016/j.bbr.2006.01.002.

    Article  PubMed  Google Scholar 

  • Gilbert, P. E., Kesner, R. P., & DeCoteau, W. E. (1998). Memory for spatial location: Role of the hippocampus in mediating spatial pattern separation. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 18(2), 804–810.

    Google Scholar 

  • Gilbert, P. E., Kesner, R. P., & Lee, I. (2001). Dissociating hippocampal subregions: Double dissociation between dentate gyrus and CA1. Hippocampus, 11(6), 626–636. doi:10.1002/hipo.1077.

    Article  PubMed  Google Scholar 

  • Good, C. D., Johnsrude, I. S., Ashburner, J., Henson, R. N., Friston, K. J., & Frackowiak, R. S. (2001). A voxel-based morphometric study of ageing in 465 normal adult human brains. NeuroImage, 14(1 Pt 1), 21–36. doi:10.1006/nimg.2001.0786.

    Article  PubMed  Google Scholar 

  • Goodrich-Hunsaker, N. J., Hunsaker, M. R., & Kesner, R. P. (2005). Dissociating the role of the parietal cortex and dorsal hippocampus for spatial information processing. Behavioral Neuroscience, 119(5), 1307–1315. doi:10.1037/0735-7044.119.5.1307.

    Article  PubMed  Google Scholar 

  • Goodrich-Hunsaker, N. J., Hunsaker, M. R., & Kesner, R. P. (2008). The interactions and dissociations of the dorsal hippocampus subregions: How the dentate gyrus, CA3, and CA1 process spatial information. Behavioral Neuroscience, 122(1), 16–26. doi:10.1037/0735-7044.122.1.16.

    Article  PubMed  Google Scholar 

  • Gracian, E. I., Shelley, L. E., Morris, A. M., & Gilbert, P. E. (2013). Age-related changes in place learning for adjacent and separate locations. Neurobiology of Aging, 34(10), 2304–2309. doi:10.1016/j.neurobiolaging.2013.03.033.

    Article  PubMed Central  PubMed  Google Scholar 

  • Hodges, J. R., Erzinçlioğlu, S., & Patterson, K. (2006). Evolution of cognitive deficits and conversion to dementia in patients with mild cognitive impairment: A very-long-term follow-up study. Dementia and Geriatric Cognitive Disorders, 21(5–6), 380–391. doi:10.1159/000092534.

    Article  PubMed  Google Scholar 

  • Holden, H. M., & Gilbert, P. E. (2012). Less efficient pattern separation may contribute to age-related spatial memory deficits. Frontiers in Aging Neuroscience, 4, 9. doi: 10.3389/fnagi.2012.00009.

    Article  PubMed Central  PubMed  Google Scholar 

  • Holden, H. M., Hoebel, C., Loftis, K., & Gilbert, P. E. (2012). Spatial pattern separation in cognitively normal young and older adults. Hippocampus, 22(9), 1826–1832. doi:10.1002/hipo.22017.

    Article  PubMed Central  PubMed  Google Scholar 

  • Holden, H. M., Toner, C., Pirogovsky, E., Kirwan, C. B., & Gilbert, P. E. (2013). Visual object pattern separation varies in older adults. Learning & Memory (Cold Spring Harbor, N.Y.), 20(7), 358–362. doi:10.1101/lm.030171.112.

    Article  Google Scholar 

  • Hunsaker, M. R., & Kesner, R. P. (2008). Evaluating the differential roles of the dorsal dentate gyrus, dorsal CA3, and dorsal CA1 during a temporal ordering for spatial locations task. Hippocampus, 18(9), 955–964. doi:10.1002/hipo.20455.

    Article  PubMed Central  PubMed  Google Scholar 

  • Hunsaker, M. R., & Kesner, R. P. (2013). The operation of pattern separation and pattern completion processes associated with different attributes or domains of memory. Neuroscience and Biobehavioral Reviews, 37(1), 36–58. doi:10.1016/j.neubiorev.2012.09.014.

    Article  PubMed  Google Scholar 

  • Hunsaker, M. R., Fieldsted, P. M., Rosenberg, J. S., & Kesner, R. P. (2008). Dissociating the roles of dorsal and ventral CA1 for the temporal processing of spatial locations, visual objects, and odors. Behavioral Neuroscience, 122(3), 643–650. doi:10.1037/0735-7044.122.3.643.

    Article  PubMed  Google Scholar 

  • Huxter, J. R., Miranda, J. A., & Dias, R. (2012). The hippocampal physiology of approaching middle-age: Early indicators of change. Hippocampus, 22(9), 1923–1940. doi:10.1002/hipo.22027.

    Article  PubMed  Google Scholar 

  • Insausti, R., Insausti, A. M., Sobreviela, M. T., Salinas, A., & Martínez-Peñuela, J. M. (1998). Human medial temporal lobe in aging: Anatomical basis of memory preservation. Microscopy Research and Technique, 43(1), 8–15. doi:10.1002/(SICI)1097-0029(19981001)43:13.0.CO;2-4.

    Article  PubMed  Google Scholar 

  • Kamboh, M. I. (2004). Molecular genetics of late-onset Alzheimer’s disease. Annals of Human Genetics, 68(Pt 4), 381–404. doi:10.1046/j.1529-8817.2004.00110.x.

    Article  PubMed  Google Scholar 

  • Kennedy, K. M., & Raz, N. (2009). Aging white matter and cognition: Differential effects of regional variations in diffusion properties on memory, executive functions, and speed. Neuropsychologia, 47(3), 916–927. doi:10.1016/j.neuropsychologia.2009.01.001.

    Article  PubMed Central  PubMed  Google Scholar 

  • Kesner, R. P. (2007). A behavioral analysis of dentate gyrus function. Progress in Brain Research, 163, 567–576. doi:10.1016/S0079-6123(07)63030-1.

    Article  PubMed  Google Scholar 

  • Kesner, R. P. (2009). Tapestry of memory. Behavioral Neuroscience, 123(1), 1–13. doi:10.1037/a0014004.

    Article  PubMed  Google Scholar 

  • Kesner, R. P. (2013a). An analysis of the dentate gyrus function. Behavioural Brain Research, 254, 1–7. doi:10.1016/j.bbr.2013.01.012.

    Article  PubMed  Google Scholar 

  • Kesner, R. P. (2013b). A process analysis of the CA3 subregion of the hippocampus. Frontiers in Cellular Neuroscience, 7, 78. doi:10.3389/fncel.2013.00078.

    Article  PubMed Central  PubMed  Google Scholar 

  • Kesner, R. P., & Gilbert, P. E. (2006). The role of the medial caudate nucleus, but not the hippocampus, in a matching-to sample task for a motor response. The European Journal of Neuroscience, 23(7), 1888–1894. doi:10.1111/j.1460-9568.2006.04709.x.

    Article  PubMed  Google Scholar 

  • Kesner, R. P., & Hopkins, R. O. (2006). Mnemonic functions of the hippocampus: a comparison between animals and humans. Biological Psychology, 73(1), 3–18. doi:10.1016/j.biopsycho.2006.01.004.

    Article  PubMed  Google Scholar 

  • Kesner, R. P., & Hunsaker, M. R. (2010). The temporal attributes of episodic memory. Behavioural Brain Research, 215(2), 299–309. doi:10.1016/j.bbr.2009.12.029.

    Article  PubMed  Google Scholar 

  • Kesner, R. P., Gilbert, P. E., & Wallenstein, G. V. (2000). Testing neural network models of memory with behavioral experiments. Current Opinion in Neurobiology, 10(2), 260–265.

    Article  PubMed  Google Scholar 

  • Kesner, R. P., Gilbert, P. E., & Barua, L. A. (2002). The role of the hippocampus in memory for the temporal order of a sequence of odors. Behavioral Neuroscience, 116(2), 286–290.

    Article  PubMed  Google Scholar 

  • Kesner, R. P., Hunsaker, M. R., & Ziegler, W. (2010). The role of the dorsal CA1 and ventral CA1 in memory for the temporal order of a sequence of odors. Neurobiology of Learning and Memory, 93(1), 111–116. doi:10.1016/j.nlm.2009.08.010.

    Article  PubMed  Google Scholar 

  • Kesner, R. P., Hunsaker, M. R., & Ziegler, W. (2011). The role of the dorsal and ventral hippocampus in olfactory working memory. Neurobiology of Learning and Memory, 96(2), 361–366. doi:10.1016/j.nlm.2011.06.011.

    Article  PubMed  Google Scholar 

  • Kirwan, C. B., & Stark, C. E. L. (2007). Overcoming interference: an fMRI investigation of pattern separation in the medial temporal lobe. Learning & Memory (Cold Spring Harbor, N.Y.), 14(9), 625–633. doi:10.1101/lm.663507.

    Article  Google Scholar 

  • Kirwan, C. B., Hartshorn, A., Stark, S. M., Goodrich-Hunsaker, N. J., Hopkins, R. O., & Stark, C. E. L. (2012). Pattern separation deficits following damage to the hippocampus. Neuropsychologia, 50(10), 2408–2414. doi:10.1016/j.neuropsychologia.2012.06.011.

    Article  PubMed Central  Google Scholar 

  • Kramer, J. H., Rosen, H. J., Du, A.-T., Schuff, N., Hollnagel, C., Weiner, M. W., Miller, B. L., et al. (2005). Dissociations in hippocampal and frontal contributions to episodic memory performance. Neuropsychology, 19(6), 799–805. doi:10.1037/0894-4105.19.6.7999.

    Article  PubMed Central  PubMed  Google Scholar 

  • Kramer, J. H., Mungas, D., Reed, B. R., Wetzel, M. E., Burnett, M. M., Miller, B. L., Weiner, M. W., et al. (2007). Longitudinal MRI and cognitive change in healthy elderly. Neuropsychology, 21(4), 412–418. doi:10.1037/0894-4105.21.4.412.

    Article  PubMed Central  PubMed  Google Scholar 

  • Kubik, S., Miyashita, T., & Guzowski, J. F. (2007). Using immediate-early genes to map hippocampal subregional functions. Learning & Memory (Cold Spring Harbor, N.Y.), 14(11), 758–770. doi:10.1101/lm.698107.

    Article  Google Scholar 

  • Kuhn, H. G., Dickinson-Anson, H., & Gage, F. H. (1996). Neurogenesis in the dentate gyrus of the adult rat: Age-related decrease of neuronal progenitor proliferation. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 16(6), 2027–2033.

    Google Scholar 

  • Lacy, J. W., Yassa, M. A., Stark, S. M., Muftuler, L. T., & Stark, C. E. L. (2011). Distinct pattern separation related transfer functions in human CA3/dentate and CA1 revealed using high-resolution fMRI and variable mnemonic similarity. Learning & Memory (Cold Spring Harbor, N.Y.), 18(1), 15–18. doi:10.1101/lm.1971111.

    Article  Google Scholar 

  • LaRocque, K. F., Smith, M. E., Carr, V. A., Witthoft, N., Grill-Spector, K., & Wagner, A. D. (2013). Global similarity and pattern separation in the human medial temporal lobe predict subsequent memory. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 33(13), 5466–5474. doi:10.1523/JNEUROSCI.4293-12.2013.

    Article  Google Scholar 

  • Lee, I., Jerman, T. S., & Kesner, R. P. (2005). Disruption of delayed memory for a sequence of spatial locations following CA1- or CA3-lesions of the dorsal hippocampus. Neurobiology of Learning and Memory, 84(2), 138–147. doi:10.1016/j.nlm.2005.06.002.

    Article  PubMed  Google Scholar 

  • Leutgeb, J. K., Leutgeb, S., Moser, M.-B., & Moser, E. I. (2007). Pattern separation in the dentate gyrus and CA3 of the hippocampus. Science (New York, N.Y.), 315(5814), 961–966. doi:10.1126/science.1135801.

    Article  Google Scholar 

  • Luu, P., Sill, O. C., Gao, L., Becker, S., Wojtowicz, J. M., & Smith, D. M. (2012). The role of adult hippocampal neurogenesis in reducing interference. Behavioral Neuroscience, 126(3), 381–391. doi:10.1037/a0028252.

    Article  PubMed Central  PubMed  Google Scholar 

  • Ly, M., Murray, E., & Yassa, M. A. (2013). Perceptual versus conceptual interference and pattern separation of verbal stimuli in young and older adults. Hippocampus, 23(6), 425–430. doi:10.1002/hipo.22110.

    Article  PubMed Central  PubMed  Google Scholar 

  • Marr, D. (1971). Simple memory: A theory for archicortex. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 262(841), 23–81.

    Article  PubMed  Google Scholar 

  • Marrone, D. F., Adams, A. A., & Satvat, E. (2011). Increased pattern separation in the aged fascia dentata. Neurobiology of Aging, 32(12), 2317.e23–2317.e32. doi:10.1016/j.neurobiolaging.2010.03.021.

    Article  PubMed  Google Scholar 

  • McDonald, R. J., & White, N. M. (1995). Hippocampal and nonhippocampal contributions to place learning in rats. Behavioral Neuroscience, 109(4), 579–593.

    Article  PubMed  Google Scholar 

  • McHugh, T. J., Jones, M. W., Quinn, J. J., Balthasar, N., Coppari, R., Elmquist, J. K., Lowell, B. B., et al. (2007). Dentate gyrus NMDA receptors mediate rapid pattern separation in the hippocampal network. Science (New York, N.Y.), 317(5834), 94–99. doi:10.1126/science.1140263.

    Article  Google Scholar 

  • McNaughton, B. L., & Nadel, L. (1990). “Hebb-Marr networks and the neurobiological representation of action in space”. In M. A. Gluck & D. E. Rumelhart (Eds.), Neuroscience and connectionist theory (pp. 1–63). Hillsdale: Erlbaum.

    Google Scholar 

  • McNaughton, B. L., Barnes, C. A., Meltzer, J., & Sutherland, R. J. (1989). Hippocampal granule cells are necessary for normal spatial learning but not for spatially-selective pyramidal cell discharge. Experimental Brain Research, 76(3), 485–496.

    Article  PubMed  Google Scholar 

  • McTighe, S. M., Mar, A. C., Romberg, C., Bussey, T. J., & Saksida, L. M. (2009). A new touchscreen test of pattern separation: effect of hippocampal lesions. Neuroreport, 20(9), 881–885. doi: 10.1097/WNR.0b013e32832c5eb2.

    Google Scholar 

  • Morris, A. M., Churchwell, J. C., Kesner, R. P., & Gilbert, P. E. (2012). Selective lesions of the dentate gyrus produce disruptions in place learning for adjacent spatial locations. Neurobiology of Learning and Memory, 97(3), 326–331. doi:10.1016/j.nlm.2012.02.005.

    Article  PubMed Central  PubMed  Google Scholar 

  • Motley, S. E., & Kirwan, C. B. (2012). A parametric investigation of pattern separation processes in the medial temporal lobe. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 32(38), 13076–13085. doi:10.1523/JNEUROSCI.5920-11.2012.

    Article  Google Scholar 

  • Moyer, J. R., Jr., & Brown, T. H. (2006). Impaired trace and contextual fear conditioning in aged rats. Behavioral Neuroscience, 120(3), 612–624. doi:10.1037/0735-7044.120.3.612.

    Article  PubMed  Google Scholar 

  • Mueller, S. G., & Weiner, M. W. (2009). Selective effect of age, Apo e4, and Alzheimer’s disease on hippocampal subfields. Hippocampus, 19(6), 558–564. doi:10.1002/hipo.20614.

    Article  PubMed Central  PubMed  Google Scholar 

  • Mueller, S. G., Schuff, N., Yaffe, K., Madison, C., Miller, B., & Weiner, M. W. (2010). Hippocampal atrophy patterns in mild cognitive impairment and Alzheimer’s disease. Human Brain Mapping, 31(9), 1339–1347. doi:10.1002/hbm.20934.

    Article  PubMed Central  PubMed  Google Scholar 

  • Mungas, D., Harvey, D., Reed, B. R., Jagust, W. J., DeCarli, C., Beckett, L., Mack, W. J., et al. (2005). Longitudinal volumetric MRI change and rate of cognitive decline. Neurology, 65(4), 565–571. doi:10.1212/01.wnl.0000172913.88973.0d.

    Article  PubMed Central  PubMed  Google Scholar 

  • Myers, C. E., & Scharfman, H. E. (2009). A role for hilar cells in pattern separation in the dentate gyrus: a computational approach. Hippocampus, 19(4), 321–337. doi:10.1002/hipo.20516.

    Article  PubMed Central  PubMed  Google Scholar 

  • Nakashiba, T., Cushman, J. D., Pelkey, K. A., Renaudineau, S., Buhl, D. L., McHugh, T. J., Rodriguez Barrera, V., et al. (2012). Young dentate granule cells mediate pattern separation, whereas old granule cells facilitate pattern completion. Cell, 149(1), 188–201. doi:10.1016/j.cell.2012.01.046.

    Article  PubMed Central  PubMed  Google Scholar 

  • Norman, G., & Eacott, M. J. (2004). Impaired object recognition with increasing levels of feature ambiguity in rats with perirhinal cortex lesions. Behavioural Brain Research, 148(1–2), 79–91.

    Article  PubMed  Google Scholar 

  • O’Reilly, R. C., & McClelland, J. L. (1994). Hippocampal conjunctive encoding, storage, and recall: Avoiding a trade-off. Hippocampus, 4(6), 661–682. doi:10.1002/hipo.450040605.

    Article  PubMed  Google Scholar 

  • Patrylo, P. R., & Williamson, A. (2007). The effects of aging on dentate circuitry and function. Progress in Brain Research, 163, 679–696. doi:10.1016/S0079-6123(07)63037-4.

    Article  PubMed  Google Scholar 

  • Penner, M. R., Roth, T. L., Chawla, M. K., Hoang, L. T., Roth, E. D., Lubin, F. D., Sweatt, J. D., et al. (2011). Age-related changes in Arc transcription and DNA methylation within the hippocampus. Neurobiology of Aging, 32(12), 2198–2210. doi:10.1016/j.neurobiolaging.2010.01.009.

    Article  PubMed Central  PubMed  Google Scholar 

  • Persson, J., Pudas, S., Lind, J., Kauppi, K., Nilsson, L.-G., & Nyberg, L. (2012). Longitudinal structure-function correlates in elderly reveal MTL dysfunction with cognitive decline. Cerebral Cortex (New York, N.Y.: 1991), 22(10), 2297–2304. doi:10.1093/cercor/bhr306.

    Article  Google Scholar 

  • Price, J. L., Ko, A. I., Wade, M. J., Tsou, S. K., McKeel, D. W., & Morris, J. C. (2001). Neuron number in the entorhinal cortex and CA1 in preclinical Alzheimer disease. Archives of Neurology, 58(9), 1395–1402.

    Article  PubMed  Google Scholar 

  • Rand-Giovannetti, E., Chua, E. F., Driscoll, A. E., Schacter, D. L., Albert, M. S., & Sperling, R. A. (2006). Hippocampal and neocortical activation during repetitive encoding in older persons. Neurobiology of Aging, 27(1), 173–182. doi:10.1016/j.neurobiolaging.2004.12.013.

    Article  PubMed  Google Scholar 

  • Rapp, P. R., & Gallagher, M. (1996). Preserved neuron number in the hippocampus of aged rats with spatial learning deficits. Proceedings of the National Academy of Sciences of the United States of America, 93(18), 9926–9930.

    Article  PubMed Central  PubMed  Google Scholar 

  • Rapp, P. R., Stack, E. C., & Gallagher, M. (1999). Morphometric studies of the aged hippocampus: I. Volumetric analysis in behaviorally characterized rats. The Journal of Comparative Neurology, 403(4), 459–470.

    Article  PubMed  Google Scholar 

  • Rapp, P. R., Deroche, P. S., Mao, Y., & Burwell, R. D. (2002). Neuron number in the parahippocampal region is preserved in aged rats with spatial learning deficits. Cerebral Cortex (New York, N.Y.: 1991), 12(11), 1171–1179.

    Article  Google Scholar 

  • Rasmussen, T., Schliemann, T., Sørensen, J. C., Zimmer, J., & West, M. J. (1996). Memory impaired aged rats: No loss of principal hippocampal and subicular neurons. Neurobiology of Aging, 17(1), 143–147.

    Article  PubMed  Google Scholar 

  • Raz, N., Gunning-Dixon, F., Head, D., Rodrigue, K. M., Williamson, A., & Acker, J. D. (2004). Aging, sexual dimorphism, and hemispheric asymmetry of the cerebral cortex: Replicability of regional differences in volume. Neurobiology of Aging, 25(3), 377–396. doi:10.1016/S0197-4580(03)00118-0.

    Article  PubMed  Google Scholar 

  • Raz, N., Lindenberger, U., Rodrigue, K. M., Kennedy, K. M., Head, D., Williamson, A., Dahle, C., et al. (2005). Regional brain changes in aging healthy adults: General trends, individual differences and modifiers. Cerebral Cortex (New York, N.Y.: 1991), 15(11), 1676–1689. doi:10.1093/cercor/bhi044.

    Article  Google Scholar 

  • Rodrigue, K. M., & Raz, N. (2004). Shrinkage of the entorhinal cortex over five years predicts memory performance in healthy adults. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 24(4), 956–963. doi:10.1523/JNEUROSCI.4166-03.2004.

    Article  Google Scholar 

  • Rolls, E T. (1996). A theory of hippocampal function in memory. Hippocampus, 6(6), 601–620. doi:10.1002/(SICI)1098-1063(1996)6:63.0.CO;2-J.

    Article  PubMed  Google Scholar 

  • Rolls, E. T. (2010). A computational theory of episodic memory formation in the hippocampus. Behavioural Brain Research, 215(2), 180–196. doi:10.1016/j.bbr.2010.03.027.

    Article  PubMed  Google Scholar 

  • Rolls, E. T., & Kesner, R. P. (2006). A computational theory of hippocampal function, and empirical tests of the theory. Progress in Neurobiology, 79(1), 1–48. doi:10.1016/j.pneurobio.2006.04.005.

    Article  PubMed  Google Scholar 

  • Ryan, L., Cardoza, J. A., Barense, M. D., Kawa, K. H., Wallentin-Flores, J., Arnold, W. T., & Alexander, G. E. (2012). Age-related impairment in a complex object discrimination task that engages perirhinal cortex. Hippocampus, 22(10), 1978–1989. doi:10.1002/hipo.22069.

    Article  PubMed Central  PubMed  Google Scholar 

  • Sahay, A., Wilson, D. A., & Hen, R. (2011). Pattern separation: a common function for new neurons in hippocampus and olfactory bulb. Neuron, 70(4), 582–588. doi:10.1016/j.neuron.2011.05.012.

    Article  PubMed Central  PubMed  Google Scholar 

  • Saunders, A. M., Strittmatter, W. J., Schmechel, D., George-Hyslop, P. H., Pericak-Vance, M. A., Joo, S. H., Rosi, B. L., et al. (1993). Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer’s disease. Neurology, 43(8), 1467–1472.

    Article  PubMed  Google Scholar 

  • Shapiro, M. L., and Olton, D. S. (1994). “Hippocampal function and interference”. In D. L. Schacter & E. Tulving (Eds.), Memory systems (pp. 141–146). London: MIT.

    Google Scholar 

  • Small, S. A., Tsai, W. Y., DeLaPaz, R., Mayeux, R., & Stern, Y. (2002). Imaging hippocampal function across the human life span: Is memory decline normal or not? Annals of Neurology, 51(3), 290–295.

    Article  PubMed  Google Scholar 

  • Small, S. A., Chawla, M. K., Buonocore, M., Rapp, P. R., & Barnes, C. A. (2004). Imaging correlates of brain function in monkeys and rats isolates a hippocampal subregion differentially vulnerable to aging. Proceedings of the National Academy of Sciences of the United States of America, 101(18), 7181–7186. doi:10.1073/pnas.0400285101.

    Article  PubMed Central  PubMed  Google Scholar 

  • Small, S. A., Schobel, S. A., Buxton, R. B., Witter, M. P., & Barnes, C. A. (2011). A pathophysiological framework of hippocampal dysfunction in ageing and disease. Nature Reviews Neuroscience, 12(10), 585–601. doi:10.1038/nrn3085.

    Article  PubMed Central  PubMed  Google Scholar 

  • Smith, T. D., Adams, M. M., Gallagher, M., Morrison, J. H., & Rapp, P. R. (2000). Circuit-specific alterations in hippocampal synaptophysin immunoreactivity predict spatial learning impairment in aged rats. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 20(17), 6587–6593.

    Google Scholar 

  • Stark, S. M., Yassa, M. A., & Stark, C. E. L. (2010). Individual differences in spatial pattern separation performance associated with healthy aging in humans. Learning & Memory (Cold Spring Harbor, N.Y.), 17(6), 284–288. doi:10.1101/lm.1768110.

    Article  Google Scholar 

  • Stark, S. M., Yassa, M. A., Lacy, J. W., & Stark, C. E. L. (2013). A task to assess behavioral pattern separation (BPS) in humans: Data from healthy aging and mild cognitive impairment. Neuropsychologia, 51, 2442–2449. doi:10.1016/j.neuropsychologia.2012.12.014.

    Article  PubMed Central  PubMed  Google Scholar 

  • Tanila, H. (1999). Hippocampal place cells can develop distinct representations of two visually identical environments. Hippocampus, 9(3), 235–246. doi:10.1002/(SICI)1098-1063(1999)9:33.0.CO;2-3.

    Article  PubMed  Google Scholar 

  • Tolentino, J. C., Pirogovsky, E., Luu, T., Toner, C. K., & Gilbert, P. E. (2012). The effect of interference on temporal order memory for random and fixed sequences in nondemented older adults. Learning & Memory (Cold Spring Harbor, N.Y.), 19(6), 251–255. doi:10.1101/lm.026062.112.

    Article  Google Scholar 

  • Toner, C. K., Pirogovsky, E., Kirwan, C. B., & Gilbert, P. E. (2009). Visual object pattern separation deficits in nondemented older adults. Learning & Memory (Cold Spring Harbor, N.Y.), 16(5), 338–342. doi:10.1101/lm.1315109.

    Article  Google Scholar 

  • Treves, A., & Rolls, E. T. (1992). Computational constraints suggest the need for two distinct input systems to the hippocampal CA3 network. Hippocampus, 2(2), 189–199. doi:10.1002/hipo.450020209.

    Article  PubMed  Google Scholar 

  • Walhovd, K. B., Fjell, A. M., Dale, A. M., McEvoy, L. K., Brewer, J., Karow, D. S., Salmon, D. P., et al. (2010). Multi-modal imaging predicts memory performance in normal aging and cognitive decline. Neurobiology of Aging, 31(7), 1107–1121. doi:10.1016/j.neurobiolaging.2008.08.013.

    Article  PubMed Central  PubMed  Google Scholar 

  • Weeden, C.S.S., Hu, N.J., Ho, L.Y.N., & Kesner, R.P. (2012). The role of the ventral dentate gyrus in olfactory learning and memory. Neuroscience Meeting Planner, Program Number 397.17/EEE39.

    Google Scholar 

  • West, M. J., Kawas, C. H., Martin, L. J., & Troncoso, J. C. (2000). The CA1 region of the human hippocampus is a hot spot in Alzheimer’s disease. Annals of the New York Academy of Sciences, 908, 255–259.

    Article  PubMed  Google Scholar 

  • Wilson, D. A. (2009). Pattern separation and completion in olfaction. Annals of the New York Academy of Sciences, 1170, 306–312. doi:10.1111/j.1749–6632.2009.04017.x.

    Article  PubMed Central  PubMed  Google Scholar 

  • Wilson, D. A., & Sullivan, R. M. (2011). Cortical processing of odor objects. Neuron, 72(4), 506–519. doi:10.1016/j.neuron.2011.10.027.

    Article  PubMed Central  PubMed  Google Scholar 

  • Wilson, I. A., Gallagher, M., Eichenbaum, H., & Tanila, H. (2006). Neurocognitive aging: Prior memories hinder new hippocampal encoding. Trends in Neurosciences, 29(12), 662–670. doi:10.1016/j.tins.2006.10.002.

    Article  PubMed Central  PubMed  Google Scholar 

  • Wu, W., Brickman, A. M., Luchsinger, J., Ferrazzano, P., Pichiule, P., Yoshita, M., Brown, T., et al. (2008). The brain in the age of old: the hippocampal formation is targeted differentially by diseases of late life. Annals of Neurology, 64(6), 698–706. doi:10.1002/ana.21557.

    Article  PubMed Central  PubMed  Google Scholar 

  • Yassa, M. A., & Stark, C. E. L. (2011). Pattern separation in the hippocampus. Trends in Neurosciences, 34(10), 515–525. doi:10.1016/j.tins.2011.06.006.

    Article  PubMed Central  PubMed  Google Scholar 

  • Yassa, M. A., Stark, S. M., Bakker, A., Albert, M. S., Gallagher, M., & Stark, C. E. L. (2010). High-resolution structural and functional MRI of hippocampal CA3 and dentate gyrus in patients with amnestic Mild Cognitive Impairment. NeuroImage, 51(3), 1242–1252. doi:10.1016/j.neuroimage.2010.03.040.

    Article  PubMed Central  PubMed  Google Scholar 

  • Yassa, M. A., Lacy, J. W., Stark, S. M., Albert, M. S., Gallagher, M., & Stark, C. E. L. (2011a). Pattern separation deficits associated with increased hippocampal CA3 and dentate gyrus activity in nondemented older adults. Hippocampus, 21(9), 968–979. doi:10.1002/hipo.20808.

    PubMed Central  PubMed  Google Scholar 

  • Yassa, M. A., Mattfeld, A. T., Stark, S. M., & Stark, C. E. L. (2011b). Age-related memory deficits linked to circuit-specific disruptions in the hippocampus. Proceedings of the National Academy of Sciences of the United States of America, 108(21), 8873–8878. doi:10.1073/pnas.1101567108.

    Article  PubMed Central  PubMed  Google Scholar 

  • Ziegler, D. A., Piguet, O., Salat, D. H., Prince, K., Connally, E., & Corkin, S. (2010). Cognition in healthy aging is related to regional white matter integrity, but not cortical thickness. Neurobiology of Aging, 31(11), 1912–1926. doi:10.1016/j.neurobiolaging.2008.10.015.

    Article  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

A portion of the research reviewed in the chapter was supported by a National Institutes of Health Grant (#AG034202) from the National Institute on Aging awarded to Paul E. Gilbert. Paul Gilbert would like to thank and acknowledge Dr. Raymond Kesner for being an excellent mentor, collaborator, and friend. Andrea Morris also would like to thank Dr. Kesner for his mentorship, valuable scientific input, and advice. The authors thank Dr. Kesner for his contributions to the field and wish him the best in his retirement.

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Authors and Affiliations

  1. Department of Psychology, San Diego State University, San Diego, CA, USA

    Prof. Paul E. Gilbert PhD & David P. Sheppard MA

  2. Joint Doctoral Program in Clinical Psychology, San Diego State University—University of California San Diego, 6363 Alvarado Court, Suite 103, 92120, San Diego, CA, USA

    Prof. Paul E. Gilbert PhD & Heather M. Holden MS

  3. Department of Psychology, University of Houston, 126 Heyne Building, Suite 204, 77004-5022, Houston, TX, USA

    David P. Sheppard MA

  4. Department of Health Policy and Management, University of California, 650 Charles Young Dr. S. 31-269, 90095, Box 951772, Los Angeles, CA, USA

    Andrea M. Morris PhD, MPH

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Correspondence to Paul E. Gilbert PhD .

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  1. Department of Psychology, Radford University, Radford, Virginia, USA

    Pamela A. Jackson

  2. Department of Cognitive Science, University of California-San Diego, La Jolla, California, USA

    Andrea A. Chiba

  3. Department of Neurological Surgery and Center for Neuroscience, University of California-Davis, Davis, California, USA

    Robert F. Berman

  4. Department of Psychology, University of Illinois at Chicago, Chicago, Illinois, USA

    Michael E. Ragozzino

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Gilbert, P., Holden, H., Sheppard, D., Morris, A. (2016). Pattern Separation: A Key Processing Deficit Associated with Aging?. In: Jackson, P., Chiba, A., Berman, R., Ragozzino, M. (eds) The Neurobiological Basis of Memory. Springer, Cham. https://doi.org/10.1007/978-3-319-15759-7_5

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