Lateral Entorhinal Cortex is Critical for Novel Object-Context Recognition

Episodic memory incorporates information about specific events or occasions including spatial locations and the contextual features of the environment in which the event took place. It has been modeled in rats using spontaneous exploration of novel configurations of objects, their locations, and the contexts in which they are presented. While we have a detailed understanding of how spatial location is processed in the brain relatively little is known about where the nonspatial contextual components of episodic memory are processed. Initial experiments measured c‐fos expression during an object‐context recognition (OCR) task to examine which networks within the brain process contextual features of an event. Increased c‐fos expression was found in the lateral entorhinal cortex (LEC; a major hippocampal afferent) during OCR relative to control conditions. In a subsequent experiment it was demonstrated that rats with lesions of LEC were unable to recognize object‐context associations yet showed normal object recognition and normal context recognition. These data suggest that contextual features of the environment are integrated with object identity in LEC and demonstrate that recognition of such object‐context associations requires the LEC. This is consistent with the suggestion that contextual features of an event are processed in LEC and that this information is combined with spatial information from medial entorhinal cortex to form episodic memory in the hippocampus. © 2013 Wiley Periodicals, Inc.

[1]  Jonathan L. C. Lee,et al.  Post-training unilateral amygdala lesions selectively impair contextual fear memories. , 2012, Learning & memory.

[2]  David M. Smith,et al.  A comparison of the effects of temporary hippocampal lesions on single and dual context versions of the olfactory sequence memory task. , 2012, Behavioral neuroscience.

[3]  Bilateral and Unilateral Hippocampal Inactivation Did not Differ in their Effect on Consolidation Processes in the Morris Water Maze , 2008, The International journal of neuroscience.

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

[5]  G. V. Van Hoesen,et al.  Perforant pathway changes and the memory impairment of Alzheimer's disease , 1986, Annals of neurology.

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

[7]  M. Mattson,et al.  Selective Vulnerability of Neurons in Layer II of the Entorhinal Cortex during Aging and Alzheimer's Disease , 2010, Neural plasticity.

[8]  Kathryn J Jeffery,et al.  Heterogeneous Modulation of Place Cell Firing by Changes in Context , 2003, The Journal of Neuroscience.

[9]  D. Mumby,et al.  Dissociation in retrograde memory for object discriminations and object recognition in rats with perirhinal cortex damage , 2002, Behavioural Brain Research.

[10]  V. Gurevich,et al.  The Nature of the Arrestin·Receptor Complex Determines the Ultimate Fate of the Internalized Receptor* , 2003, The Journal of Biological Chemistry.

[11]  K. Jeffery,et al.  How heterogeneous place cell responding arises from homogeneous grids—A contextual gating hypothesis , 2008, Hippocampus.

[12]  P. Winn,et al.  Bar pressing for food: differential consequences of lesions to the anterior versus posterior pedunculopontine , 2009, The European journal of neuroscience.

[13]  H. Eichenbaum,et al.  Hippocampal Neurons Encode Information about Different Types of Memory Episodes Occurring in the Same Location , 2000, Neuron.

[14]  B. McNaughton,et al.  Independent Codes for Spatial and Episodic Memory in Hippocampal Neuronal Ensembles , 2005, Science.

[15]  M. Hasselmo,et al.  Spatial Representations of Hippocampal CA1 Neurons Are Modulated by Behavioral Context in a Hippocampus-Dependent Memory Task , 2007, The Journal of Neuroscience.

[16]  Michael E. Hasselmo,et al.  Runaway synaptic modification in models of cortex: Implications for Alzheimer's disease , 1994, Neural Networks.

[17]  H. Braak,et al.  Alzheimer's disease affects limbic nuclei of the thalamus , 2004, Acta Neuropathologica.

[18]  M. Witter,et al.  Cellular properties of principal neurons in the rat entorhinal cortex. I. The lateral entorhinal cortex , 2012, Hippocampus.

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

[20]  M. Shapiro,et al.  Prospective and Retrospective Memory Coding in the Hippocampus , 2003, Neuron.

[21]  James J Knierim,et al.  Lateral entorhinal neurons are not spatially selective in cue‐rich environments , 2011, Hippocampus.

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

[23]  P. Andersen,et al.  Spatial learning impairment parallels the magnitude of dorsal hippocampal lesions, but is hardly present following ventral lesions , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[24]  Cullen B. Owens,et al.  Spatial representations in dorsal hippocampal neurons during a tactile‐visual conditional discrimination task , 2012, Hippocampus.

[25]  H. Eichenbaum,et al.  Towards a functional organization of episodic memory in the medial temporal lobe , 2012, Neuroscience & Biobehavioral Reviews.

[26]  J. Knierim,et al.  Major Dissociation Between Medial and Lateral Entorhinal Input to Dorsal Hippocampus , 2005, Science.

[27]  R. Morris,et al.  Glutamate-receptor-mediated encoding and retrieval of paired-associate learning , 2003, Nature.

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

[29]  M. J. Wade,et al.  Neuron number in the entorhinal cortex and CA1 in preclinical Alzheimer disease. , 2001, Archives of neurology.

[30]  Trygve B. Leergaard,et al.  Digital Atlas of Anatomical Subdivisions and Boundaries of the Rat Hippocampal Region , 2010, Front. Neuroinform..

[31]  M. Eacott,et al.  Dissociable effects of lesions to the perirhinal cortex and the postrhinal cortex on memory for context and objects in rats. , 2005, Behavioral neuroscience.

[32]  E. Esposito,et al.  The Unilateral Nigral Lesion Induces Dramatic Bilateral Modification on Rat Brain Monoamine Neurochemistry , 2009, Annals of the New York Academy of Sciences.

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

[34]  M. Hasselmo A model of episodic memory: Mental time travel along encoded trajectories using grid cells , 2009, Neurobiology of Learning and Memory.

[35]  Malcolm W. Brown,et al.  Cholinergic Neurotransmission Is Essential for Perirhinal Cortical Plasticity and Recognition Memory , 2003, Neuron.

[36]  I. Fried,et al.  Internally Generated Reactivation of Single Neurons in Human Hippocampus During Free Recall , 2008, Science.

[37]  J. Guzowski,et al.  Using immediate-early genes to map hippocampal subregional functions. , 2007, Learning & memory.

[38]  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.

[39]  M. Chun,et al.  Memory deficits for implicit contextual information in amnesic subjects with hippocampal damage , 1999, Nature Neuroscience.

[40]  E. Tolman Cognitive maps in rats and men. , 1948, Psychological review.

[41]  L. Swanson The Rat Brain in Stereotaxic Coordinates, George Paxinos, Charles Watson (Eds.). Academic Press, San Diego, CA (1982), vii + 153, $35.00, ISBN: 0 125 47620 5 , 1984 .

[42]  Craig E L Stark,et al.  Intrinsic functional connectivity of the human medial temporal lobe suggests a distinction between adjacent MTL cortices and hippocampus , 2012, Hippocampus.

[43]  H. Soininen,et al.  Subfield- and layer-specific changes in parvalbumin, calretinin and calbindin-D28k immunoreactivity in the entorhinal cortex in Alzheimer's disease , 1999, Neuroscience.

[44]  J. Ainge,et al.  Induction of c‐fos in specific thalamic nuclei following stimulation of the pedunculopontine tegmental nucleus , 2004, The European journal of neuroscience.

[45]  A. Dickinson,et al.  Episodic-like memory during cache recovery by scrub jays , 1998, Nature.

[46]  Richard G M Morris,et al.  Longitudinal axis of the hippocampus: Both septal and temporal poles of the hippocampus support water maze spatial learning depending on the training protocol , 2003, Hippocampus.

[47]  Stephanie J. Babb,et al.  Episodic-like Memory in the Rat , 2006, Current Biology.

[48]  B. Knowlton,et al.  Remembering episodes: a selective role for the hippocampus during retrieval , 2000, Nature Neuroscience.

[49]  J. Knierim,et al.  Hippocampal place cells: Parallel input streams, subregional processing, and implications for episodic memory , 2006, Hippocampus.

[50]  B. Richmond,et al.  Role of perirhinal cortex in object perception, memory, and associations , 2001, Current Opinion in Neurobiology.

[51]  Stephen Maren,et al.  Pavlovian fear conditioning as a behavioral assay for hippocampus and amygdala function: cautions and caveats , 2008, The European journal of neuroscience.

[52]  M. Moser,et al.  Distributed Encoding and Retrieval of Spatial Memory in the Hippocampus , 1998, The Journal of Neuroscience.

[53]  F. Wörgötter,et al.  Hippocampal place cells encode intended destination, and not a discriminative stimulus, in a conditional T‐maze task , 2012, Hippocampus.

[54]  M. Mishkin,et al.  Differential effects of early hippocampal pathology on episodic and semantic memory. , 1997, Science.

[55]  Matthew A Wilson,et al.  Firing Rate Dynamics in the Hippocampus Induced by Trajectory Learning , 2008, The Journal of Neuroscience.

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

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

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

[59]  Sachin S. Deshmukh,et al.  Representation of Non-Spatial and Spatial Information in the Lateral Entorhinal Cortex , 2011, Front. Behav. Neurosci..

[60]  J. Morris,et al.  Profound Loss of Layer II Entorhinal Cortex Neurons Occurs in Very Mild Alzheimer’s Disease , 1996, The Journal of Neuroscience.

[61]  M. Moser,et al.  Reduced fear expression after lesions of the ventral hippocampus , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[62]  T. Bussey,et al.  Functionally Dissociating Aspects of Event Memory: the Effects of Combined Perirhinal and Postrhinal Cortex Lesions on Object and Place Memory in the Rat , 1999, The Journal of Neuroscience.

[63]  Emma R Wood,et al.  Associative recognition and the hippocampus: Differential effects of hippocampal lesions on object‐place, object‐context and object‐place‐context memory , 2009, Hippocampus.

[64]  E. Save,et al.  Distinct roles of medial and lateral entorhinal cortex in spatial cognition. , 2013, Cerebral cortex.

[65]  M. Witter,et al.  What Does the Anatomical Organization of the Entorhinal Cortex Tell Us? , 2008, Neural plasticity.

[66]  J. Rawlins,et al.  Double dissociation of function within the hippocampus: spatial memory and hyponeophagia. , 2002, Behavioral neuroscience.

[67]  Matthew L. Shapiro,et al.  Motivational states activate distinct hippocampal representations to guide goal-directed behaviors , 2009, Proceedings of the National Academy of Sciences.

[68]  M. Tamosiunaite,et al.  Hippocampal CA1 Place Cells Encode Intended Destination on a Maze with Multiple Choice Points , 2007, The Journal of Neuroscience.

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

[70]  Sachin S. Deshmukh,et al.  Perirhinal cortex represents nonspatial, but not spatial, information in rats foraging in the presence of objects: Comparison with lateral entorhinal cortex , 2012, Hippocampus.

[71]  M. Eacott,et al.  Behavioral / Systems / Cognitive Integrated Memory for Object , Place , and Context in Rats : A Possible Model of Episodic-Like Memory ? , 2004 .