Assessment of Topographic Memory in Mice in a Complex Environment Using the Hamlet Test

Here we provide instructions to measure topographic memory in mice using the Hamlet test, a complex environment. The apparatus mimics a small hamlet with a central agora and five houses, which are functionalized since mice can drink, eat pellets, hide within a small maze, run in an activity wheel, or interact with a stranger mouse behind a grid. The houses are interconnected through a network of streets in a five‐arm star shape, and a video tracking system takes information from the activity in each house or follows a single mouse by trajectometry. Training the mice in the Hamlet, in groups for several hours per day over several days or weeks, allows consolidation of topographic memory (i.e., route learning involving both allocentric and egocentric strategies). Analysis of topographic memory can be performed a posteriori in a probe test by depriving mice of water or food and measuring their ability to efficiently reach the “eat” or “drink” house. Control groups include mice tested in non‐deprived condition and mice naïve to the Hamlet and tested in deprived or non‐deprived conditions. The present article details the apparatus, procedures, and protocols that can be used to reliably habituate mice in this complex environment and measure topographic memory. © 2018 by John Wiley & Sons, Inc.

[1]  Jean-Christophe Cassel,et al.  The double-H maze test, a novel, simple, water-escape memory task: Acquisition, recall of recent and remote memory, and effects of systemic muscarinic or NMDA receptor blockade during training , 2011, Behavioural Brain Research.

[2]  M. Wilson,et al.  NMDA receptors, place cells and hippocampal spatial memory , 2004, Nature Reviews Neuroscience.

[3]  T. Shiga,et al.  An enriched environment increases noradrenaline concentration in the mouse brain , 2002, Brain Research.

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

[5]  I. Yaniv,et al.  Environmental enrichment in mice decreases anxiety, attenuates stress responses and enhances natural killer cell activity , 2004, The European journal of neuroscience.

[6]  B L McNaughton,et al.  Dynamics of the hippocampal ensemble code for space. , 1993, Science.

[7]  R. M. Escorihuela,et al.  Environmental enrichment effects in social investigation in rats are gender dependent , 2006, Behavioural Brain Research.

[8]  C. Barnes Memory deficits associated with senescence: a neurophysiological and behavioral study in the rat. , 1979, Journal of comparative and physiological psychology.

[9]  C. Martínez-Cué,et al.  Both increases in immature dentate neuron number and decreases of immobility time in the forced swim test occurred in parallel after environmental enrichment of mice , 2007, Neuroscience.

[10]  Kuo-ping Huang,et al.  Environmental Enrichment Enhances Neurogranin Expression and Hippocampal Learning and Memory But Fails to Rescue the Impairments of Neurogranin Null Mutant Mice , 2006, The Journal of Neuroscience.

[11]  F. Volkmar,et al.  Pattern of dendritic branching in occipital cortex of rats reared in complex environments. , 1973, Experimental neurology.

[12]  B. McNaughton,et al.  Reactivation of hippocampal ensemble memories during sleep. , 1994, Science.

[13]  M. D’Esposito,et al.  Topographical disorientation: a synthesis and taxonomy. , 1999, Brain : a journal of neurology.

[14]  I. Izquierdo,et al.  Differential effect of posttraining naloxone, β-endorphin, leu-enkephalin and electroconvulsive shock administration upon memory of an open-field habituation and of a water-finding task , 1986, Psychoneuroendocrinology.

[15]  Jacqueline N. Crawley,et al.  A Proposed Test Battery and Constellations of Specific Behavioral Paradigms to Investigate the Behavioral Phenotypes of Transgenic and Knockout Mice , 1997, Hormones and Behavior.

[16]  N. Cowan What are the differences between long-term, short-term, and working memory? , 2008, Progress in brain research.

[17]  Patricia Mesa-Gresa,et al.  Potential benefits and limitations of enriched environments and cognitive activity on age-related behavioural decline. , 2012, Current topics in behavioral neurosciences.

[18]  H. Hirase,et al.  Transformation of cortical and hippocampal neural circuit by environmental enrichment , 2014, Neuroscience.

[19]  Donald K. Ingram,et al.  Complex maze learning in rodents as a model of age-related memory impairment , 1988, Neurobiology of Aging.

[20]  Hanna Damasio,et al.  The neuroanatomical correlates of route learning impairment , 2000, Neuropsychologia.

[21]  J. Goodhouse,et al.  Enrichment induces structural changes and recovery from nonspatial memory deficits in CA1 NMDAR1-knockout mice , 2000, Nature Neuroscience.

[22]  Gerd Kempermann,et al.  Experience-Induced Neurogenesis in the Senescent Dentate Gyrus , 1998, The Journal of Neuroscience.

[23]  Morris Moscovitch,et al.  A study of remote spatial memory in aged rats , 2010, Neurobiology of Aging.

[24]  Neil Burgess,et al.  Navigation expertise and the human hippocampus: A structural brain imaging analysis , 2003, Hippocampus.

[25]  F. Trousse,et al.  Topographical memory analyzed in mice using the Hamlet test, a novel complex maze , 2018, Neurobiology of Learning and Memory.

[26]  L. Galvan,et al.  Hyposensitivity to the amnesic effects of scopolamine or amyloid beta(25-35) peptide in heterozygous acetylcholinesterase knockout (AChE(+/-)) mice. , 2008, Chemico-biological interactions.

[27]  L. Galvan,et al.  Behavioral phenotyping of heterozygous acetylcholinesterase knockout (AChE+/−) mice showed no memory enhancement but hyposensitivity to amnesic drugs , 2010, Behavioural Brain Research.

[28]  B. Winblad,et al.  Increased expression of brain-derived neurotrophic factor mRNA in rat hippocampus is associated with improved spatial memory and enriched environment , 1992, Neuroscience Letters.

[29]  R. Galani,et al.  The behavioral effects of enriched housing are not altered by serotonin depletion but enrichment alters hippocampal neurochemistry , 2007, Neurobiology of Learning and Memory.

[30]  R. Morris,et al.  Place navigation impaired in rats with hippocampal lesions , 1982, Nature.

[31]  Mitsuru Kawamura,et al.  Pure Topographical Disorientation —The Anatomical Basis of Landmark Agnosia , 2002, Cortex.

[32]  M. During,et al.  Environmental enrichment exerts sex-specific effects on emotionality in C57BL/6J mice , 2011, Behavioural Brain Research.

[33]  A. Hannan,et al.  Enriched environments, experience-dependent plasticity and disorders of the nervous system , 2006, Nature Reviews Neuroscience.

[34]  L. Feig,et al.  Long-lasting and transgenerational effects of an environmental enrichment on memory formation , 2011, Brain Research Bulletin.

[35]  J. Loeffler,et al.  Late-Life Environmental Enrichment Induces Acetylation Events and Nuclear Factor κB-Dependent Regulations in the Hippocampus of Aged Rats Showing Improved Plasticity and Learning , 2016, The Journal of Neuroscience.

[36]  Morris Moscovitch,et al.  An investigation of the effects of hippocampal lesions in rats on pre‐ and postoperatively acquired spatial memory in a complex environment , 2010, Hippocampus.

[37]  Jean-Christophe Cassel,et al.  Environmental Enrichment Duration Differentially Affects Behavior and Neuroplasticity in Adult Mice. , 2015, Cerebral cortex.

[38]  W. Greenough,et al.  Evidence for active synapse formation or altered postsynaptic metabolism in visual cortex of rats reared in complex environments. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[39]  E. Alleva,et al.  Social deprivation stress is a triggering factor for the emergence of anxiety- and depression-like behaviours and leads to reduced brain BDNF levels in C57BL/6J mice , 2012, Psychoneuroendocrinology.

[40]  F. Gage,et al.  More hippocampal neurons in adult mice living in an enriched environment , 1997, Nature.

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

[42]  M. Sarter,et al.  Attenuation of scopolamine-induced impairment of spontaneous alternation behaviour by antagonist but not inverse agonist and agonist β-carbolines , 2004, Psychopharmacology.

[43]  M. Diamond,et al.  Increased length of terminal dendritic segments in old adult rats' somatosensory cortex: An environmentally induced response , 1982, Experimental Neurology.

[44]  Morris Moscovitch,et al.  Preserved spatial memory after hippocampal lesions: effects of extensive experience in a complex environment , 2005, Nature Neuroscience.

[45]  J. Tsien,et al.  Differential effects of enrichment on learning and memory function in NR2B transgenic mice , 2001, Neuropharmacology.

[46]  A. Sirigu,et al.  Pure Topographical Disorientation: A Definition and Anatomical Basis , 1987, Cortex.

[47]  A. Hannan,et al.  Review: Environmental enrichment and brain repair: harnessing the therapeutic effects of cognitive stimulation and physical activity to enhance experience‐dependent plasticity , 2014, Neuropathology and applied neurobiology.

[48]  A. Holmes,et al.  Behavioral profiles of inbred strains on novel olfactory, spatial and emotional tests for reference memory in mice , 2002, Genes, brain, and behavior.

[49]  G. Teuchert-Noodt,et al.  Epigenetic factors differentially influence postnatal maturation of serotonin (5-HT) innervation in cerebral cortex of gerbils: interaction of rearing conditions and early methamphetamine challenge. , 2003, Brain research. Developmental brain research.

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

[51]  V. Baumans,et al.  Effect of enrichment on variation and results in the light/dark test , 2003, Laboratory animals.

[52]  K. Wada,et al.  Enriched environments influence depression-related behavior in adult mice and the survival of newborn cells in their hippocampi , 2007, Behavioural Brain Research.

[53]  T. Maurice,et al.  Cognitive impairments in adult mice with constitutive inactivation of RIP140 gene expression , 2012, Genes, brain, and behavior.

[54]  Alain Berthoz,et al.  Impaired Sequential Egocentric and Allocentric Memories in Forebrain-Specific–NMDA Receptor Knock-Out Mice during a New Task Dissociating Strategies of Navigation , 2006, The Journal of Neuroscience.

[55]  C. Rampon,et al.  New neurons in the dentate gyrus are involved in the expression of enhanced long‐term memory following environmental enrichment , 2005, The European journal of neuroscience.