Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

Science 305 (5688): 1295-1298

Copyright © 2004 by the American Association for the Advancement of Science

Distinct Ensemble Codes in Hippocampal Areas CA3 and CA1

Stefan Leutgeb,1 Jill K. Leutgeb,1 Alessandro Treves,1,2 May-Britt Moser,1 Edvard I. Moser1*

Abstract: The hippocampus has differentiated into an extensively connected recurrent stage (CA3) followed by a feed-forward stage (CA1). We examined the function of this structural differentiation by determining how cell ensembles in rat CA3 and CA1 generate representations of rooms with common spatial elements. In CA3, distinct subsets of pyramidal cells were activated in each room, regardless of the similarity of the testing enclosure. In CA1, the activated populations overlapped, and the overlap increased in similar enclosures. After exposure to a novel room, ensemble activity developed slower in CA3 than CA1, suggesting that the representations emerged independently.

1 Centre for the Biology of Memory, Medical-Technical Research Centre, Norwegian University of Science and Technology, 7489 Trondheim, Norway.
2 Cognitive Neuroscience Sector, International School for Advanced Studies, Trieste, Italy.

Back to Top

Note added in proof: Additional evidence for CA1-CA3 differences is provided by a recent study measuring immediate early gene activation in two different novel rooms (36).

* To whom correspondence should be addressed. E-mail: edvard.moser{at}cbm.ntnu.no


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Memory consolidation in humans: new evidence and opportunities.
E. A. Maguire (2014)
Exp Physiol 99, 471-486
   Abstract »    Full Text »    PDF »
Space in the brain: how the hippocampal formation supports spatial cognition.
T. Hartley, C. Lever, N. Burgess, and J. O'Keefe (2014)
Phil Trans R Soc B 369, 20120510
   Abstract »    Full Text »    PDF »
Encoding of Head Direction by Hippocampal Place Cells in Bats.
A. Rubin, M. M. Yartsev, and N. Ulanovsky (2014)
J. Neurosci. 34, 1067-1080
   Abstract »    Full Text »    PDF »
A {theta}-{gamma} Oscillation Code for Neuronal Coordination during Motor Behavior.
J. Igarashi, Y. Isomura, K. Arai, R. Harukuni, and T. Fukai (2013)
J. Neurosci. 33, 18515-18530
   Abstract »    Full Text »    PDF »
Distinct Hippocampal Time Cell Sequences Represent Odor Memories in Immobilized Rats.
C. J. MacDonald, S. Carrow, R. Place, and H. Eichenbaum (2013)
J. Neurosci. 33, 14607-14616
   Abstract »    Full Text »    PDF »
Evidence for Encoding versus Retrieval Scheduling in the Hippocampus by Theta Phase and Acetylcholine.
V. Douchamps, A. Jeewajee, P. Blundell, N. Burgess, and C. Lever (2013)
J. Neurosci. 33, 8689-8704
   Abstract »    Full Text »    PDF »
Distinct Dendritic Arborization and In Vivo Firing Patterns of Parvalbumin-Expressing Basket Cells in the Hippocampal Area CA3.
J. J. Tukker, B. Lasztoczi, L. Katona, J. D. B. Roberts, E. K. Pissadaki, Y. Dalezios, L. Marton, L. Zhang, T. Klausberger, and P. Somogyi (2013)
J. Neurosci. 33, 6809-6825
   Abstract »    Full Text »    PDF »
Selection of distinct populations of dentate granule cells in response to inputs as a mechanism for pattern separation in mice.
W. Deng, M. Mayford, and F. H. Gage (2013)
eLife Sci 2, e00312
   Abstract »    Full Text »    PDF »
Grid cell firing patterns signal environmental novelty by expansion.
C. Barry, L. L. Ginzberg, J. O'Keefe, and N. Burgess (2012)
PNAS 109, 17687-17692
   Abstract »    Full Text »    PDF »
A Parametric Investigation of Pattern Separation Processes in the Medial Temporal Lobe.
S. E. Motley and C. B. Kirwan (2012)
J. Neurosci. 32, 13076-13084
   Abstract »    Full Text »    PDF »
Reward Cues in Space: Commonalities and Differences in Neural Coding by Hippocampal and Ventral Striatal Ensembles.
C. S. Lansink, J. C. Jackson, J. V. Lankelma, R. Ito, T. W. Robbins, B. J. Everitt, and C. M. A. Pennartz (2012)
J. Neurosci. 32, 12444-12459
   Abstract »    Full Text »    PDF »
Spatial Information Outflow from the Hippocampal Circuit: Distributed Spatial Coding and Phase Precession in the Subiculum.
S. M. Kim, S. Ganguli, and L. M. Frank (2012)
J. Neurosci. 32, 11539-11558
   Abstract »    Full Text »    PDF »
Sound sensitivity of neurons in rat hippocampus during performance of a sound-guided task.
P. M. Itskov, E. Vinnik, C. Honey, J. Schnupp, and M. E. Diamond (2012)
J Neurophysiol 107, 1822-1834
   Abstract »    Full Text »    PDF »
Hippocampal Dynamics Predict Interindividual Cognitive Differences in Rats.
V. Hok, E. Chah, R. B. Reilly, and S. M. O'Mara (2012)
J. Neurosci. 32, 3540-3551
   Abstract »    Full Text »    PDF »
Remembering to Learn: Independent Place and Journey Coding Mechanisms Contribute to Memory Transfer.
A. S. Bahar and M. L. Shapiro (2012)
J. Neurosci. 32, 2191-2203
   Abstract »    Full Text »    PDF »
Terminal Field and Firing Selectivity of Cholecystokinin-Expressing Interneurons in the Hippocampal CA3 Area.
B. Lasztoczi, J. J. Tukker, P. Somogyi, and T. Klausberger (2011)
J. Neurosci. 31, 18073-18093
   Abstract »    Full Text »    PDF »
Decoding overlapping memories in the medial temporal lobes using high-resolution fMRI.
M. J. Chadwick, D. Hassabis, and E. A. Maguire (2011)
Learn. Mem. 18, 742-746
   Abstract »    Full Text »    PDF »
Hippocampal Polysynaptic Computation.
R. Kimura, S. Kang, N. Takahashi, A. Usami, N. Matsuki, T. Fukai, and Y. Ikegaya (2011)
J. Neurosci. 31, 13168-13179
   Abstract »    Full Text »    PDF »
A stable hippocampal representation of a space requires its direct experience.
D. C. Rowland, Y. Yanovich, and C. G. Kentros (2011)
PNAS 108, 14654-14658
   Abstract »    Full Text »    PDF »
Memory-Guided Learning: CA1 and CA3 Neuronal Ensembles Differentially Encode the Commonalities and Differences between Situations.
A. S. Bahar, P. R. Shirvalkar, and M. L. Shapiro (2011)
J. Neurosci. 31, 12270-12281
   Abstract »    Full Text »    PDF »
Modular Realignment of Entorhinal Grid Cell Activity as a Basis for Hippocampal Remapping.
J. D. Monaco and L. F. Abbott (2011)
J. Neurosci. 31, 9414-9425
   Abstract »    Full Text »    PDF »
Age-related memory deficits linked to circuit-specific disruptions in the hippocampus.
M. A. Yassa, A. T. Mattfeld, S. M. Stark, and C. E. L. Stark (2011)
PNAS 108, 8873-8878
   Abstract »    Full Text »    PDF »
Distinct pattern separation related transfer functions in human CA3/dentate and CA1 revealed using high-resolution fMRI and variable mnemonic similarity.
J. W. Lacy, M. A. Yassa, S. M. Stark, L. T. Muftuler, and C. E. L. Stark (2010)
Learn. Mem. 18, 15-18
   Abstract »    Full Text »    PDF »
Experience-Dependent Development of Coordinated Hippocampal Spatial Activity Representing the Similarity of Related Locations.
A. C. Singer, M. P. Karlsson, A. R. Nathe, M. F. Carr, and L. M. Frank (2010)
J. Neurosci. 30, 11586-11604
   Abstract »    Full Text »    PDF »
Attractor-Map Versus Autoassociation Based Attractor Dynamics in the Hippocampal Network.
L. L. Colgin, S. Leutgeb, K. Jezek, J. K. Leutgeb, E. I. Moser, B. L. McNaughton, and M.-B. Moser (2010)
J Neurophysiol 104, 35-50
   Abstract »    Full Text »    PDF »
Individual differences in spatial pattern separation performance associated with healthy aging in humans.
S. M. Stark, M. A. Yassa, and C. E. L. Stark (2010)
Learn. Mem. 17, 284-288
   Abstract »    Full Text »    PDF »
Hebbian Analysis of the Transformation of Medial Entorhinal Grid-Cell Inputs to Hippocampal Place Fields.
F. Savelli and J. J. Knierim (2010)
J Neurophysiol 103, 3167-3183
   Abstract »    Full Text »    PDF »
Attention-Like Modulation of Hippocampus Place Cell Discharge.
A. A. Fenton, W. W. Lytton, J. M. Barry, P. P. Lenck-Santini, L. E. Zinyuk, S. Kubik, J. Bures, B. Poucet, R. U. Muller, and A. V. Olypher (2010)
J. Neurosci. 30, 4613-4625
   Abstract »    Full Text »    PDF »
Mitochondrial DNA Toxicity in Forebrain Neurons Causes Apoptosis, Neurodegeneration, and Impaired Behavior.
K. H. Lauritzen, O. Moldestad, L. Eide, H. Carlsen, G. Nesse, J. F. Storm, I. M. Mansuy, L. H. Bergersen, and A. Klungland (2010)
Mol. Cell. Biol. 30, 1357-1367
   Abstract »    Full Text »    PDF »
Distinct roles for dorsal CA3 and CA1 in memory for sequential nonspatial events.
A. Farovik, L. M. Dupont, and H. Eichenbaum (2010)
Learn. Mem. 17, 12-17
   Abstract »    Full Text »    PDF »
Accuracy of hippocampal network activity is disrupted by neuroinflammation: rescue by memantine.
S. Rosi, V. Ramirez-Amaya, A. Vazdarjanova, E. E. Esparza, P. B. Larkin, J. R. Fike, G. L. Wenk, and C. A. Barnes (2009)
Brain 132, 2464-2477
   Abstract »    Full Text »    PDF »
A Code for Spatial Alternation During Fixation in Rat Hippocampal CA1 Neurons.
M. Takahashi, J. Lauwereyns, Y. Sakurai, and M. Tsukada (2009)
J Neurophysiol 102, 556-567
   Abstract »    Full Text »    PDF »
The Multiple Origins and Laminar Topography of the Hippocampal Theta Rhythm.
P. Shirvalkar and A. S. Bahar (2009)
J. Neurosci. 29, 7111-7113
   Full Text »    PDF »
Visual object pattern separation deficits in nondemented older adults.
C. K. Toner, E. Pirogovsky, C. B. Kirwan, and P. E. Gilbert (2009)
Learn. Mem. 16, 338-342
   Abstract »    Full Text »    PDF »
A Specific Role of the Human Hippocampus in Recall of Temporal Sequences.
H. Lehn, H.-A. Steffenach, N. M. van Strien, D. J. Veltman, M. P. Witter, and A. K. Haberg (2009)
J. Neurosci. 29, 3475-3484
   Abstract »    Full Text »    PDF »
Vasopressin 1b Receptor Knock-Out Impairs Memory for Temporal Order.
L. M. DeVito, R. Konigsberg, C. Lykken, M. Sauvage, W. S. Young III, and H. Eichenbaum (2009)
J. Neurosci. 29, 2676-2683
   Abstract »    Full Text »    PDF »
Network Dynamics Underlying the Formation of Sparse, Informative Representations in the Hippocampus.
M. P. Karlsson and L. M. Frank (2008)
J. Neurosci. 28, 14271-14281
   Abstract »    Full Text »    PDF »
Rapid encoding of new information alters the profile of plasticity-related mRNA transcripts in the hippocampal CA3 region.
R. P. Haberman, H. J. Lee, C. Colantuoni, M. T. Koh, and M. Gallagher (2008)
PNAS 105, 10601-10606
   Abstract »    Full Text »    PDF »
Finite Scale of Spatial Representation in the Hippocampus.
K. B. Kjelstrup, T. Solstad, V. H. Brun, T. Hafting, S. Leutgeb, M. P. Witter, E. I. Moser, and M.-B. Moser (2008)
Science 321, 140-143
   Abstract »    Full Text »    PDF »
NEUROSCIENCE: Detailed Differences.
S. Leutgeb (2008)
Science 319, 1623-1624
   Abstract »    Full Text »    PDF »
Pattern Separation in the Human Hippocampal CA3 and Dentate Gyrus.
A. Bakker, C. B. Kirwan, M. Miller, and C. E. L. Stark (2008)
Science 319, 1640-1642
   Abstract »    Full Text »    PDF »
Qualitatively Different Hippocampal Subfield Engagement Emerges with Mastery of a Spatial Memory Task by Rats.
G. L. Poirier, E. Amin, and J. P. Aggleton (2008)
J. Neurosci. 28, 1034-1045
   Abstract »    Full Text »    PDF »
Modulation of CA3 Afferent Inputs by Novelty and Theta Rhythm.
D. M. Villarreal, A. L. Gross, and B. E. Derrick (2007)
J. Neurosci. 27, 13457-13467
   Abstract »    Full Text »    PDF »
The Medial Prefrontal Cortex Is Involved in Spatial Memory Retrieval under Partial-Cue Conditions.
Y. S. Jo, E. H. Park, I. H. Kim, S. K. Park, H. Kim, H. T. Kim, and J.-S. Choi (2007)
J. Neurosci. 27, 13567-13578
   Abstract »    Full Text »    PDF »
Pattern separation, pattern completion, and new neuronal codes within a continuous CA3 map.
S. Leutgeb and J. K. Leutgeb (2007)
Learn. Mem. 14, 745-757
   Abstract »    Full Text »    PDF »
Using immediate-early genes to map hippocampal subregional functions.
S. Kubik, T. Miyashita, and J. F. Guzowski (2007)
Learn. Mem. 14, 758-770
   Abstract »    Full Text »    PDF »
Arc length coding by interference of theta frequency oscillations may underlie context-dependent hippocampal unit data and episodic memory function.
M. E. Hasselmo (2007)
Learn. Mem. 14, 782-794
   Abstract »    Full Text »    PDF »
Memory retrieval time and memory capacity of the CA3 network: Role of gamma frequency oscillations.
L. de Almeida, M. Idiart, and J. E. Lisman (2007)
Learn. Mem. 14, 795-806
   Abstract »    Full Text »    PDF »
Stress-induced alterations in hippocampal plasticity, place cells, and spatial memory.
J. J. Kim, H. J. Lee, A. C. Welday, E. Song, J. Cho, P. E. Sharp, M. W. Jung, and H. T. Blair (2007)
PNAS 104, 18297-18302
   Abstract »    Full Text »    PDF »
Neural Ensembles in CA3 Transiently Encode Paths Forward of the Animal at a Decision Point.
A. Johnson and A. D. Redish (2007)
J. Neurosci. 27, 12176-12189
   Abstract »    Full Text »    PDF »
Overcoming interference: An fMRI investigation of pattern separation in the medial temporal lobe.
C. B. Kirwan and C. E.L. Stark (2007)
Learn. Mem. 14, 625-633
   Abstract »    Full Text »    PDF »
NEUROSCIENCE: Remembering the Subtle Differences.
D. M. Bannerman and R. Sprengel (2007)
Science 317, 50-51
   Abstract »    Full Text »    PDF »
Dentate Gyrus NMDA Receptors Mediate Rapid Pattern Separation in the Hippocampal Network.
T. J. McHugh, M. W. Jones, J. J. Quinn, N. Balthasar, R. Coppari, J. K. Elmquist, B. B. Lowell, M. S. Fanselow, M. A. Wilson, and S. Tonegawa (2007)
Science 317, 94-99
   Abstract »    Full Text »    PDF »
Recruitment of an inhibitory hippocampal network after bursting in a single granule cell.
M. Mori, B. H. Gahwiler, and U. Gerber (2007)
PNAS 104, 7640-7645
   Abstract »    Full Text »    PDF »
Pattern Separation in the Dentate Gyrus and CA3 of the Hippocampus.
J. K. Leutgeb, S. Leutgeb, M.-B. Moser, and E. I. Moser (2007)
Science 315, 961-966
   Abstract »    Full Text »    PDF »
The functional nature of synaptic circuitry is altered in area CA3 of the hippocampus in a mouse model of Down's syndrome.
J. E. Hanson, M. Blank, R. A. Valenzuela, C. C. Garner, and D. V. Madison (2007)
J. Physiol. 579, 53-67
   Abstract »    Full Text »    PDF »
Disconnection analysis of CA3 and DG in mediating encoding but not retrieval in a spatial maze learning task.
T. Jerman, R. P. Kesner, and M. R. Hunsaker (2006)
Learn. Mem. 13, 458-464
   Abstract »    Full Text »    PDF »
Temperature-dependent shift of balance among the components of short-term plasticity in hippocampal synapses..
V. A. Klyachko and C. F. Stevens (2006)
J. Neurosci. 26, 6945-6957
   Abstract »    Full Text »    PDF »
A spin glass model of path integration in rat medial entorhinal cortex..
M. C. Fuhs and D. S. Touretzky (2006)
J. Neurosci. 26, 4266-4276
   Abstract »    Full Text »    PDF »
The Role of CA3 Hippocampal NMDA Receptors in Paired Associate Learning.
T. Rajji, D. Chapman, H. Eichenbaum, and R. Greene (2006)
J. Neurosci. 26, 908-915
   Abstract »    Full Text »    PDF »
Hippocampal CA1 Circuitry Dynamically Gates Direct Cortical Inputs Preferentially at Theta Frequencies.
C. W. Ang, G. C. Carlson, and D. A. Coulter (2005)
J. Neurosci. 25, 9567-9580
   Abstract »    Full Text »    PDF »
Topography of Arc/Arg3.1 mRNA Expression in the Dorsal and Ventral Hippocampus Induced by Recent and Remote Spatial Memory Recall: Dissociation of CA3 and CA1 Activation.
P. A. Gusev, C. Cui, D. L. Alkon, and A. N. Gubin (2005)
J. Neurosci. 25, 9384-9397
   Abstract »    Full Text »    PDF »
Behavioral Evidence That Segregation and Representation Are Dissociable Hippocampal Functions.
S. Kubik and A. A. Fenton (2005)
J. Neurosci. 25, 9205-9212
   Abstract »    Full Text »    PDF »
Independent Codes for Spatial and Episodic Memory in Hippocampal Neuronal Ensembles.
S. Leutgeb, J. K. Leutgeb, C. A. Barnes, E. I. Moser, B. L. McNaughton, and M.-B. Moser (2005)
Science 309, 619-623
   Abstract »    Full Text »    PDF »
Age-Associated Alterations of Hippocampal Place Cells Are Subregion Specific.
I. A. Wilson, S. Ikonen, M. Gallagher, H. Eichenbaum, and H. Tanila (2005)
J. Neurosci. 25, 6877-6886
   Abstract »    Full Text »    PDF »
Attractor Dynamics in the Hippocampal Representation of the Local Environment.
T. J. Wills, C. Lever, F. Cacucci, N. Burgess, and J. O'Keefe (2005)
Science 308, 873-876
   Abstract »    Full Text »    PDF »
Dissociable contributions within the medial temporal lobe to encoding of object-location associations.
T. Sommer, M. Rose, J. Glascher, T. Wolbers, and C. Buchel (2005)
Learn. Mem. 12, 343-351
   Abstract »    Full Text »    PDF »
NEUROSCIENCE: In the Place Space.
D. K. Bilkey (2004)
Science 305, 1245-1246
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882