The Rodent Hippocampus Is Essential for Nonspatial Object Memory

Elucidating the role of the rodent hippocampus in object recognition memory is critical for establishing the appropriateness of rodents as models of human memory and for their use in the development of memory disorder treatments. In mammals, spatial memory and nonspatial memory depend upon the hippocampus and associated medial temporal lobe (MTL) structures. Although well established in humans, the role of the rodent hippocampus in object memory remains highly debated due to conflicting findings across temporary and permanent hippocampal lesion studies and evidence that the perirhinal cortex may support object memory. In the current studies, we used intrahippocampal muscimol microinfusions to transiently inactivate the male C57BL/6J mouse hippocampus at distinct stages during the novel object recognition (NOR) task: during object memory encoding and consolidation, just consolidation, and/or retrieval. We also assessed the effect of temporary hippocampal inactivation when objects were presented in different contexts, thus eliminating the spatial or contextual components of the task. Lastly, we assessed extracellular dorsal hippocampal glutamate efflux and firing properties of hippocampal neurons while mice performed the NOR task. Our results reveal a clear and compelling role of the rodent hippocampus in nonspatial object memory.

[1]  D. Bilkey,et al.  Instability in the Place Field Location of Hippocampal Place Cells after Lesions Centered on the Perirhinal Cortex , 2001, The Journal of Neuroscience.

[2]  H. Eichenbaum,et al.  Recollection-like memory retrieval in rats is dependent on the hippocampus , 2004, Nature.

[3]  Rosemary A. Cowell,et al.  Double Dissociation between the Effects of Peri-Postrhinal Cortex and Hippocampal Lesions on Tests of Object Recognition and Spatial Memory: Heterogeneity of Function within the Temporal Lobe , 2004, The Journal of Neuroscience.

[4]  Brian J. Wiltgen,et al.  Context Fear Learning in the Absence of the Hippocampus , 2006, The Journal of Neuroscience.

[5]  Jerry W Rudy,et al.  Context representations, context functions, and the parahippocampal-hippocampal system. , 2009, Learning & memory.

[6]  R. Muller,et al.  Further study of the control of place cell firing by intra‐apparatus objects , 1999, Hippocampus.

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

[8]  R. Clark,et al.  The medial temporal lobe. , 2004, Annual review of neuroscience.

[9]  R. Burwell The Parahippocampal Region: Corticocortical Connectivity , 2000, Annals of the New York Academy of Sciences.

[10]  Larry R Squire,et al.  Spatial memory, recognition memory, and the hippocampus. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[11]  R. Clark,et al.  Recognition memory and the medial temporal lobe: a new perspective , 2007, Nature Reviews Neuroscience.

[12]  Boyer D. Winters,et al.  Object recognition memory: Neurobiological mechanisms of encoding, consolidation and retrieval , 2008, Neuroscience & Biobehavioral Reviews.

[13]  R. Clark,et al.  Rats with lesions of the hippocampus are impaired on the delayed nonmatching‐to‐sample task † , 2001, Hippocampus.

[14]  Emilio Kropff,et al.  Place cells, grid cells, and the brain's spatial representation system. , 2008, Annual review of neuroscience.

[15]  R. Clark,et al.  Impaired Recognition Memory in Monkeys after Damage Limited to the Hippocampal Region , 2000, The Journal of Neuroscience.

[16]  T. Bussey,et al.  Transient Inactivation of Perirhinal Cortex Disrupts Encoding, Retrieval, and Consolidation of Object Recognition Memory , 2005, The Journal of Neuroscience.

[17]  S. J. Martin,et al.  Reversible neural inactivation reveals hippocampal participation in several memory processes , 1999, Nature Neuroscience.

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

[19]  P. Dudchenko The hippocampus as a cognitive map , 2010 .

[20]  D. Mumby,et al.  Hippocampal damage and exploratory preferences in rats: memory for objects, places, and contexts. , 2002, Learning & memory.

[21]  R. Roesler,et al.  Temporary inactivation reveals an essential role of the dorsal hippocampus in consolidation of object recognition memory , 2006, Neuroscience Letters.

[22]  M. Cossette,et al.  A limited role for the hippocampus in the modulation of novel-object preference by contextual cues. , 2008, Learning & memory.

[23]  R. Williams,et al.  Genetic architecture of the mouse hippocampus: identification of gene loci with selective regional effects , 2003, Genes, brain, and behavior.

[24]  Benjamin A. Dunn,et al.  Grid cells require excitatory drive from the hippocampus , 2013, Nature Neuroscience.

[25]  T. Bussey,et al.  Hippocampal lesions that abolish spatial maze performance spare object recognition memory at delays of up to 48 hours , 2005, Hippocampus.

[26]  R. Stackman,et al.  On the delay-dependent involvement of the hippocampus in object recognition memory , 2004, Neurobiology of Learning and Memory.

[27]  H. Eichenbaum,et al.  Dynamics of Hippocampal and Cortical Activation during Consolidation of a Nonspatial Memory , 2006, The Journal of Neuroscience.

[28]  D. Mumby,et al.  Retrograde and anterograde object recognition in rats with hippocampal lesions , 2003, Hippocampus.

[29]  J. Bachevalier,et al.  The Hippocampal/Parahippocampal Regions and Recognition Memory: Insights from Visual Paired Comparison versus Object-Delayed Nonmatching in Monkeys , 2004, The Journal of Neuroscience.

[30]  R. Clark,et al.  Object recognition memory and the rodent hippocampus. , 2010, Learning & memory.

[31]  D. Mumby,et al.  Hippocampal damage and anterograde object‐recognition in rats after long retention intervals , 2005, Hippocampus.

[32]  Howard Eichenbaum,et al.  A cognitive map for object memory in the hippocampus. , 2009, Learning & memory.

[33]  Sophie L. Dix,et al.  Extending the spontaneous preference test of recognition: evidence of object-location and object-context recognition , 1999, Behavioural Brain Research.

[34]  T. Abel,et al.  Post-training reversible inactivation of the hippocampus enhances novel object recognition memory. , 2010, Learning & memory.

[35]  Robert E. Clark,et al.  Impaired Recognition Memory in Rats after Damage to the Hippocampus , 2000, The Journal of Neuroscience.

[36]  Martín Cammarota,et al.  On the role of hippocampal protein synthesis in the consolidation and reconsolidation of object recognition memory. , 2007, Learning & memory.

[37]  O. Pascalis,et al.  Neonatal aspiration lesions of the hippocampal formation impair visual recognition memory when assessed by paired‐comparison task but not by delayed nonmatching‐to‐sample task , 1999, Hippocampus.

[38]  M. Meunier,et al.  Stimulus similarity and encoding time influence incidental recognition memory in adult monkeys with selective hippocampal lesions. , 2011, Learning & memory.

[39]  H. Eichenbaum,et al.  The medial temporal lobe and recognition memory. , 2007, Annual review of neuroscience.

[40]  Malcolm W. Brown,et al.  Recognition memory: What are the roles of the perirhinal cortex and hippocampus? , 2001, Nature Reviews Neuroscience.

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

[42]  H. Eichenbaum Hippocampus Cognitive Processes and Neural Representations that Underlie Declarative Memory , 2004, Neuron.

[43]  U. Rutishauser,et al.  Activity of human hippocampal and amygdala neurons during retrieval of declarative memories , 2008, Proceedings of the National Academy of Sciences.

[44]  George Paxinos,et al.  The Mouse Brain in Stereotaxic Coordinates , 2001 .

[45]  H. Eichenbaum,et al.  Neuronal activity in the hippocampus during delayed non‐match to sample performance in rats: Evidence for hippocampal processing in recognition memory , 1992, Hippocampus.

[46]  Emma R Wood,et al.  The role of the hippocampus in object recognition in rats: Examination of the influence of task parameters and lesion size , 2006, Behavioural Brain Research.

[47]  G. Barker,et al.  When Is the Hippocampus Involved in Recognition Memory? , 2011, The Journal of Neuroscience.

[48]  T. Bussey,et al.  Distinct patterns of behavioural impairments resulting from fornix transection or neurotoxic lesions of the perirhinal and postrhinal cortices in the rat , 2000, Behavioural Brain Research.

[49]  G. Paxinos,et al.  Comprar The Mouse Brain in Stereotaxic Coordinates, The coronal plates and diagrams Compact, 3rd Edition | Keith Franklin | 9780123742445 | Academic Press , 2008 .

[50]  David Wood,et al.  Luddites must not block progress in genetics , 1999, Nature.

[51]  R. C. Honey,et al.  Context- but not familiarity-dependent forms of object recognition are impaired following excitotoxic hippocampal lesions in rats. , 2007, Behavioral neuroscience.

[52]  H. Eichenbaum,et al.  Critical role of the hippocampus in memory for sequences of events , 2002, Nature Neuroscience.

[53]  S. Floresco,et al.  Disruption of spatial but not object-recognition memory by neurotoxic lesions of the dorsal hippocampus in rats. , 1997, Behavioral neuroscience.

[54]  H. Eichenbaum,et al.  The global record of memory in hippocampal neuronal activity , 1999, Nature.