Aging and KIBRA/WWC1 genotype affect spatial memory processes in a virtual navigation task

Spatial navigation relies on multiple mnemonic mechanisms and previous work in younger adults has described two separate types of spatial memory. One type uses directional as well as boundary‐related information for spatial memory and mainly implicates the hippocampal formation. The other type has been linked to directional and landmark‐related information and primarily involves the striatum. Using a virtual reality navigation paradigm, we studied the impacts of aging and a single nucleotide polymorphism (SNP rs17070145) of the KIBRA gene (official name: WWC1) on these memory forms. Our data showed that older adult's spatial learning was preferentially related to processing of landmark information, whereas processing of boundary information played a more prominent role in younger adults. Moreover, among older adults T‐allele carriers of the examined KIBRA polymorphism showed better spatial learning compared to C homozygotes. Together these findings provide the first evidence for an effect of the KIBRA rs17070145 polymorphism on spatial memory in humans and age differences in the reliance on landmark and boundary‐related spatial information. © 2013 Wiley Periodicals, Inc.

[1]  C. Gross,et al.  Diminished adult neurogenesis in the marmoset brain precedes old age , 2007, Proceedings of the National Academy of Sciences.

[2]  M. Kenward,et al.  Small sample inference for fixed effects from restricted maximum likelihood. , 1997, Biometrics.

[3]  F. Jessen,et al.  KIBRA gene variants are associated with episodic memory in healthy elderly , 2008, Neurobiology of Aging.

[4]  Gerd Kempermann,et al.  Why New Neurons? Possible Functions for Adult Hippocampal Neurogenesis , 2002, The Journal of Neuroscience.

[5]  N. Burgess,et al.  Geometric determinants of human spatial memory , 2004, Cognition.

[6]  S. Sikström,et al.  Aging cognition: from neuromodulation to representation , 2001, Trends in Cognitive Sciences.

[7]  H. Eichenbaum,et al.  Brain Aging: Impaired Coding of Novel Environmental Cues , 1997, The Journal of Neuroscience.

[8]  Christian F. Doeller,et al.  Parallel striatal and hippocampal systems for landmarks and boundaries in spatial memory , 2008, Proceedings of the National Academy of Sciences.

[9]  Irene E. Nagel,et al.  Human Aging Magnifies Genetic Effects on Executive Functioning and Working Memory , 2008, Frontiers in human neuroscience.

[10]  Lin Tian,et al.  Functional imaging of hippocampal place cells at cellular resolution during virtual navigation , 2010, Nature Neuroscience.

[11]  Lars Bäckman,et al.  Activation in striatum and medial temporal lobe during sequence learning in younger and older adults: Relations to performance , 2010, NeuroImage.

[12]  Hauke R. Heekeren,et al.  Age-Related Decline in Brain Resources Modulates Genetic Effects on Cognitive Functioning , 2008, Front. Neurosci..

[13]  M. Gallagher,et al.  Severity of spatial learning impairment in aging: development of a learning index for performance in the Morris water maze. , 1993, Behavioral neuroscience.

[14]  Ulman Lindenberger,et al.  Quantitative and qualitative sex differences in spatial navigation. , 2007, Scandinavian journal of psychology.

[15]  N. Raz,et al.  Extrahippocampal contributions to age differences in human spatial navigation. , 2007, Cerebral cortex.

[16]  E. Maguire,et al.  The Well-Worn Route and the Path Less Traveled Distinct Neural Bases of Route Following and Wayfinding in Humans , 2003, Neuron.

[17]  N. Burgess Spatial Cognition and the Brain , 2008, Annals of the New York Academy of Sciences.

[18]  Anders M. Dale,et al.  Consistent neuroanatomical age-related volume differences across multiple samples , 2011, Neurobiology of Aging.

[19]  L. Nilsson Memory function in normal aging , 2003, Acta neurologica Scandinavica. Supplementum.

[20]  Hauke R. Heekeren,et al.  Dopaminergic Gene Polymorphisms Affect Long-term Forgetting in Old Age: Further Support for the Magnification Hypothesis , 2013, Journal of Cognitive Neuroscience.

[21]  S. Resnick,et al.  Age differences in spatial memory in a virtual environment navigation task , 2001, Neurobiology of Aging.

[22]  L. Nadel,et al.  The Hippocampus as a Cognitive Map , 1978 .

[23]  J. Barton,et al.  Age differences in the formation and use of cognitive maps , 2009, Behavioural Brain Research.

[24]  S. Resnick,et al.  Effects of age on virtual environment place navigation and allocentric cognitive mapping. , 2002, Behavioral neuroscience.

[25]  Christian F. Doeller,et al.  The role of landmarks and boundaries in the development of spatial memory. , 2009, Developmental science.

[26]  Hauke R. Heekeren,et al.  Ebbinghaus Revisited: Influences of the BDNF Val66Met Polymorphism on Backward Serial Recall Are Modulated by Human Aging , 2010, Journal of Cognitive Neuroscience.

[27]  S. Johannsen,et al.  Temporal-spatial expression and novel biochemical properties of the memory-related protein KIBRA , 2008, Neuroscience.

[28]  G. Xavier,et al.  Loss of CA1 cells following global ischaemia correlates with spatial deficits in the circular platform task , 1998, Journal of Neuroscience Methods.

[29]  K. Jeffery,et al.  Experience-dependent rescaling of entorhinal grids , 2007, Nature Neuroscience.

[30]  G. Dawson,et al.  Age-related neural activity during allocentric spatial memory , 2009, Memory.

[31]  S. Schwab,et al.  KIBRA genetic polymorphism influences episodic memory in later life, but does not increase the risk of mild cognitive impairment , 2008, Journal of cellular and molecular medicine.

[32]  Richard S. J. Frackowiak,et al.  Knowing where and getting there: a human navigation network. , 1998, Science.

[33]  M. Packard,et al.  Differential effects of fornix and caudate nucleus lesions on two radial maze tasks: evidence for multiple memory systems , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[34]  B. Thelma,et al.  Dopaminergic gene polymorphisms and cognitive function in a north Indian schizophrenia cohort. , 2013, Journal of psychiatric research.

[35]  Thomas Wolbers,et al.  Ageing effects on path integration and landmark navigation , 2012, Hippocampus.

[36]  Thomas Wolbers,et al.  Maladaptive Bias for Extrahippocampal Navigation Strategies in Aging Humans , 2013, The Journal of Neuroscience.

[37]  J. O’Keefe,et al.  Neuronal computations underlying the firing of place cells and their role in navigation , 1996, Hippocampus.

[38]  David S. Olton,et al.  Hippocampal Function and Memory for Temporal Context , 1986 .

[39]  D. Howard,et al.  Age differences in learning serial patterns: direct versus indirect measures. , 1989, Psychology and aging.

[40]  B. McNaughton,et al.  Multistability of cognitive maps in the hippocampus of old rats , 1997, Nature.

[41]  Roberto Cabeza,et al.  Age-related dedifferentiation of learning systems: an fMRI study of implicit and explicit learning , 2011, Neurobiology of Aging.

[42]  J. Taube The head direction signal: origins and sensory-motor integration. , 2007, Annual review of neuroscience.

[43]  T. Hafting,et al.  Microstructure of a spatial map in the entorhinal cortex , 2005, Nature.

[44]  Lars-Göran Nilsson,et al.  KIBRA Polymorphism Is Related to Enhanced Memory and Elevated Hippocampal Processing , 2011, The Journal of Neuroscience.

[45]  J. O’Keefe,et al.  Geometric determinants of the place fields of hippocampal neurons , 1996, Nature.

[46]  Irene E. Nagel,et al.  Aging magnifies the effects of dopamine transporter and D2 receptor genes on backward serial memory , 2013, Neurobiology of Aging.

[47]  Shauna M. Stark,et al.  Age-related memory deficits linked to circuit-specific disruptions in the hippocampus , 2011, Proceedings of the National Academy of Sciences.

[48]  Onofre Combarros,et al.  Age-dependent association of KIBRA genetic variation and Alzheimer's disease risk , 2009, Neurobiology of Aging.

[49]  H. Eichenbaum,et al.  Brain Aging: Changes in the Nature of Information Coding by the Hippocampus , 1997, The Journal of Neuroscience.

[50]  J. D. McGaugh,et al.  Double dissociation of fornix and caudate nucleus lesions on acquisition of two water maze tasks: further evidence for multiple memory systems. , 1992, Behavioral neuroscience.

[51]  J. Pearce,et al.  Spatial Learning Based on Boundaries in Rats Is Hippocampus-Dependent and Prone to Overshadowing , 2010, Behavioral neuroscience.

[52]  Cheryl L. Dahle,et al.  Regional brain changes in aging healthy adults: general trends, individual differences and modifiers. , 2005, Cerebral cortex.

[53]  Neil Burgess,et al.  Distinct error-correcting and incidental learning of location relative to landmarks and boundaries , 2008, Proceedings of the National Academy of Sciences.

[54]  W E Skaggs,et al.  The Effect of Aging on Experience-Dependent Plasticity of Hippocampal Place Cells , 1997, The Journal of Neuroscience.

[55]  G. Pike,et al.  Evidence for a virtual human analog of a rodent relational memory task: A study of aging and fMRI in young adults , 2012, Hippocampus.

[56]  D. Tank,et al.  Membrane potential dynamics of grid cells , 2013, Nature.

[57]  Xiaoqian J Chai,et al.  Sex differences in directional cue use in a virtual landscape. , 2009, Behavioral neuroscience.

[58]  G. Kempermann,et al.  Adult-Generated Hippocampal Neurons Allow the Flexible Use of Spatially Precise Learning Strategies , 2009, PloS one.

[59]  John M. Pearce,et al.  Hippocampal lesions disrupt navigation based on cognitive maps but not heading vectors , 1998, Nature.

[60]  M. Heil,et al.  Spatial knowledge acquisition in younger and elderly adults: a study in a virtual environment. , 2010, Experimental psychology.

[61]  T. Palmer,et al.  Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[62]  F. Lou,et al.  KIBRA genetic polymorphism and cognitive dysfunction in depression , 2015, Psychiatry Research.

[63]  Hans-Jochen Heinze,et al.  Association of KIBRA with episodic and working memory: A meta‐analysis , 2012, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[64]  Viola S. Störmer,et al.  Dopaminergic and cholinergic modulations of visual-spatial attention and working memory: insights from molecular genetic research and implications for adult cognitive development. , 2012, Developmental psychology.

[65]  R. Passingham The hippocampus as a cognitive map J. O'Keefe & L. Nadel, Oxford University Press, Oxford (1978). 570 pp., £25.00 , 1979, Neuroscience.

[66]  R. J. McDonald,et al.  Parallel information processing in the water maze: evidence for independent memory systems involving dorsal striatum and hippocampus. , 1994, Behavioral and neural biology.

[67]  Tom R. Gaunt,et al.  American Journal of Epidemiology Practice of Epidemiology Hardy-weinberg Equilibrium Testing of Biological Ascertainment for Mendelian Randomization Studies , 2022 .

[68]  B Poucet,et al.  Medial prefrontal lesions in the rat and spatial navigation: evidence for impaired planning. , 1995, Behavioral neuroscience.

[69]  Lars Farde,et al.  Age-related dopamine D2/D3 receptor loss in extrastriatal regions of the human brain , 2000, Neurobiology of Aging.

[70]  Elizabeth M. Zelinski,et al.  Memory for spatial information in young and old adults. , 1983 .

[71]  S. Moffat Aging and Spatial Navigation: What Do We Know and Where Do We Go? , 2009, Neuropsychology Review.

[72]  John D E Gabrieli,et al.  A longitudinal study of implicit and explicit memory in old persons. , 2004, Psychology and aging.

[73]  Christian F. Doeller,et al.  Evidence for grid cells in a human memory network , 2010, Nature.

[74]  Ulman Lindenberger,et al.  Environmental topography and postural control demands shape aging-associated decrements in spatial navigation performance. , 2005, Psychology and aging.

[75]  Jason J. Corneveaux,et al.  Common Kibra Alleles Are Associated with Human Memory Performance , 2006, Science.

[76]  Véronique D. Bohbot,et al.  Spatial navigational strategies correlate with gray matter in the hippocampus of healthy older adults tested in a virtual maze , 2013, Front. Ag. Neurosci..

[77]  Jakub Hort,et al.  Spatial navigation—a unique window into physiological and pathological aging , 2012, Front. Ag. Neurosci..

[78]  Hans-Jochen Heinze,et al.  Cortical thickness changes following spatial navigation training in adulthood and aging , 2012, NeuroImage.

[79]  Ira Driscoll,et al.  The Aging Hippocampus: Navigating Between Rat and Human Experiments , 2005, Reviews in the neurosciences.

[80]  André A Fenton,et al.  PKMζ Maintains Spatial, Instrumental, and Classically Conditioned Long-Term Memories , 2008, PLoS biology.

[81]  Chandan J. Vaidya,et al.  White matter integrity correlates of implicit sequence learning in healthy aging , 2011, Neurobiology of Aging.

[82]  S. Resnick,et al.  Age differences in the neural systems supporting human allocentric spatial navigation , 2006, Neurobiology of Aging.

[83]  S. Moffat,et al.  Effects of age on navigation strategy , 2012, Neurobiology of Aging.

[84]  Wolfgang Prinz,et al.  Transformations in the Couplings Among Intellectual Abilities and Constituent Cognitive Processes Across the Life Span , 2004, Psychological science.

[85]  Shu-Chen Li,et al.  KIBRA and CLSTN2 polymorphisms exert interactive effects on human episodic memory , 2010, Neuropsychologia.

[86]  John A. King,et al.  How vision and movement combine in the hippocampal place code , 2012, Proceedings of the National Academy of Sciences.

[87]  V. Bohbot,et al.  The brain-derived neurotrophic factor Val66Met polymorphism is associated with reduced functional magnetic resonance imaging activity in the hippocampus and increased use of caudate nucleus-dependent strategies in a human virtual navigation task , 2011, The European journal of neuroscience.

[88]  J. O'Keefe,et al.  The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat. , 1971, Brain research.

[89]  Giuseppe Iaria,et al.  Hippocampal function and spatial memory: evidence from functional neuroimaging in healthy participants and performance of patients with medial temporal lobe resections. , 2004, Neuropsychology.

[90]  Thomas Wolbers,et al.  Aging specifically impairs switching to an allocentric navigational strategy , 2012, Front. Ag. Neurosci..

[91]  U Ruotsalainen,et al.  Decrease in Human Striatal Dopamine D2 Receptor Density with Age: A PET Study with [11C]Raclopride , 1993, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[92]  H. Eichenbaum,et al.  Discordance of spatial representation in ensembles of hippocampal place cells , 1997, Hippocampus.

[93]  Giuseppe Iaria,et al.  Gray Matter Differences Correlate with Spontaneous Strategies in a Human Virtual Navigation Task , 2007, The Journal of Neuroscience.

[94]  Yee Lee Shing,et al.  Aging Neuroscience , 2022 .

[95]  Gerd Kempermann,et al.  The neurogenic reserve hypothesis: what is adult hippocampal neurogenesis good for? , 2008, Trends in Neurosciences.

[96]  M. Häusser,et al.  Cellular mechanisms of spatial navigation in the medial entorhinal cortex , 2013, Nature Neuroscience.

[97]  A. Barnekow,et al.  KIBRA is a novel substrate for protein kinase Czeta. , 2004, Biochemical and biophysical research communications.

[98]  Rebecca Burwell,et al.  Severity of spatial learning impairment in aging: Development of a learning index for performance in the Morris water maze. , 1993, Behavioral neuroscience.

[99]  Armin Schneider,et al.  Frontiers in Aging Neuroscience Aging Neuroscience Review Article the Kibra Gene and Protein , 2022 .