Hippocampal output area CA1 broadcasts a generalized novelty signal during an object-place recognition task
Open accessAbstract
Animals display an innate preference for novelty, spending more time exploring both novel objects and familiar objects in novel locations. This increase in exploration is thought to allow the animal to gather the information necessary to encode new experiences. Despite extensive evidence that increased exploration following spatial change requires the hippocampus, the pattern of hippocampal activity that supports this behavior remains unknown. We examined activity in hippocampal output area CA1 and one synapse upstream in area CA3 while freely behaving rats performed an object-place recognition task. We found that the presence of novelty substantially altered activity in CA1, but not in CA3. During exploration of displaced familiar objects and novel objects in unexpected locations, CA1 place cells showed robust increases in firing rate. These firing rate increases persisted during sharp wave ripples, when place cell representations of previous experiences are replayed. Unexpectedly, increases in CA1 activity were not spatially restricted to regions of the environment that underwent change, indicating a generalized novelty signal. We suggest that hippocampal area CA1 broadcasts the presence of novelty, rather than signaling what is novel, and simultaneously becomes more plastic, allowing the integration of new information into previously stored memories.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
CA1 firing rate was increased during the OPP test, especially when a novel object was placed at a new location.
“CA1 firing rate was also increased during the OPP test, especially when a novel object was placed at a new location (Larkin et al., 2014).”
From The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties (2020) · cites this paper as Larkin et al., 2014
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
(1978) · UA Campus Repository (The University of Arizona) · Cited by 8,010 · see citing works
The Hippocampus as a Cognitive Map
Ranck, J. B. (1979) · American Journal of Psychiatry · doi:10.1176/ajp.136.10.1353 · Cited by 2,373 · see citing works
Dynamics of the Hippocampal Ensemble Code for Space
Wilson, M. A., & McNaughton, B. L. (1993) · Science · doi:10.1126/science.8351520 · Cited by 2,350 · see citing works
Place units in the hippocampus of the freely moving rat
O'Keefe, J. (1976) · Experimental Neurology · doi:10.1016/0014-4886(76)90055-8 · Cited by 1,836 · see citing works
Two-stage model of memory trace formation: A role for “noisy” brain states
Buzsáki, G. (1989) · Neuroscience · doi:10.1016/0306-4522(89)90423-5 · Cited by 1,709 · see citing works
When Is the Hippocampus Involved in Recognition Memory?
Barker, G. R. I., & Warburton, E. C. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.6413-10.2011 · Cited by 818 · see citing works
The reorganization and reactivation of hippocampal maps predict spatial memory performance
Dupret, D., O'Neill, J., Pleydell-Bouverie, B., & Csicsvari, J. (2010) · Nature Neuroscience · doi:10.1038/nn.2599 · Cited by 769 · see citing works
Hippocampal damage and exploratory preferences in rats: memory for objects, places, and contexts
Mumby, D. G., Gaskin, S., Glenn, M. J., Schramek, T. E., & Lehmann, H. (2002) · Learning & Memory · doi:10.1101/lm.41302 · Cited by 714 · see citing works
The pharmacology, neuroanatomy and neurogenetics of one-trial object recognition in rodents
Dere, E., Huston, J. P., & Silva, M. A. D. S. (2007) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2007.01.005 · Cited by 669 · see citing works
Hippocampal CA3 NMDA Receptors Are Crucial for Memory Acquisition of One-Time Experience
Nakazawa, K., Sun, L. D., Quirk, M. C., Rondi‐Reig, L., Wilson, M. A., & Tonegawa, S. (2003) · Neuron · doi:10.1016/s0896-6273(03)00165-x · Cited by 506 · see citing works
Transgenic inhibition of synaptic transmission reveals role of CA3 output in hippocampal learning
Nakashiba, T., Young, J. Z., McHugh, T. J., Buhl, D. L., & Tonegawa, S. (2008) · Science · doi:10.1126/science.1151120 · Cited by 492 · see citing works
Representation of Non-Spatial and Spatial Information in the Lateral Entorhinal Cortex
Deshmukh, S. S., & Knierim, J. J. (2011) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2011.00069 · Cited by 454 · see citing works
Hippocampal Plasticity across Multiple Days of Exposure to Novel Environments
Frank, L. M., Stanley, G. B., & Brown, E. N. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.1958-04.2004 · Cited by 410 · see citing works
Self-citationLisman, J. E., & Otmakhova, N. A. (2001) · Hippocampus · doi:10.1002/hipo.1071 · Cited by 402 · see citing works
Rewarded Outcomes Enhance Reactivation of Experience in the Hippocampus
Singer, A. C., & Frank, L. M. (2009) · Neuron · doi:10.1016/j.neuron.2009.11.016 · Cited by 385 · see citing works
Self-citationSave, É., Poucet, B., Foreman, N., & Buhot, M.-C. (1992) · Behavioral Neuroscience · doi:10.1037/0735-7044.106.3.447 · Cited by 383 · see citing works
Ylinen, A., Soltész, I., Bragin, A., Penttonen, M., Attila Gabor, S. I. K., & Buzsáki, G. (1995) · Hippocampus · doi:10.1002/hipo.450050110 · Cited by 383 · see citing works
Neuronal code for extended time in the hippocampus
Mankin, E. A., Sparks, F. T., Slayyeh, B., Sutherland, R. J., Leutgeb, S., & Leutgeb, J. K. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1214107109 · Cited by 371 · see citing works
A Model of Spatial Map Formation in the Hippocampus of the Rat
Blum, K. I., & Abbott, L. F. (1996) · Neural Computation · doi:10.1162/neco.1996.8.1.85 · Cited by 352 · see citing works
Reactivation of experience-dependent cell assembly patterns in the hippocampus
O'Neill, J., Senior, T. J., Allen, K., Huxter, J. R., & Csicsvari, J. (2008) · Nature Neuroscience · doi:10.1038/nn2037 · Cited by 318 · see citing works
Traces of experience in the lateral entorhinal cortex
Tsao, A., Moser, M.-B., & Moser, E. I. (2013) · Current Biology · doi:10.1016/j.cub.2013.01.036 · Cited by 290 · see citing works
New Experiences Enhance Coordinated Neural Activity in the Hippocampus
Cheng, S., & Frank, L. M. (2008) · Neuron · doi:10.1016/j.neuron.2007.11.035 · Cited by 286 · see citing works
Self-citationHippocampal CA3 Output Is Crucial for Ripple-Associated Reactivation and Consolidation of Memory
Nakashiba, T., Buhl, D. L., McHugh, T. J., & Tonegawa, S. (2009) · Neuron · doi:10.1016/j.neuron.2009.05.013 · Cited by 281 · see citing works
Sustained increase in hippocampal sharp-wave ripple activity during slow-wave sleep after learning
Eschenko, O., Ramadan, W., Mölle, M., Born, J., & Sara, S. J. (2008) · Learning & Memory · doi:10.1101/lm.726008 · Cited by 277 · see citing works
Singer, A. C., Carr, M. F., Karlsson, M. P., & Frank, L. M. (2013) · Neuron · doi:10.1016/j.neuron.2013.01.027 · Cited by 270 · see citing works
Self-citationTransient Slow Gamma Synchrony Underlies Hippocampal Memory Replay
Carr, M. F., Karlsson, M. P., & Frank, L. M. (2012) · Neuron · doi:10.1016/j.neuron.2012.06.014 · Cited by 255 · see citing works
Self-citationA cognitive map for object memory in the hippocampusPreprint
Manns, J. R., & Eichenbaum, H. (2009) · Learning & Memory · doi:10.1101/lm.1484509 · Cited by 240 · see citing works
Lateral entorhinal cortex is critical for novel object‐context recognition
Wilson, D. I. G., Langston, R. F., Schlesiger, M. I., Wagner, M. A., Watanabe, S., & Ainge, J. A. (2013) · Hippocampus · doi:10.1002/hipo.22095 · Cited by 232 · see citing works
Post-training reversible inactivation of the hippocampus enhances novel object recognition memory
Oliveira, A. M. M., Hawk, J. D., Abel, T., & Havekes, R. (2010) · Learning & Memory · doi:10.1101/lm.1625310 · Cited by 222 · see citing works
Network Dynamics Underlying the Formation of Sparse, Informative Representations in the Hippocampus
Karlsson, M. P., & Frank, L. M. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.4261-08.2008 · Cited by 217 · see citing works
Self-citationInfluence of local objects on hippocampal representations: Landmark vectors and memory
Deshmukh, S. S., & Knierim, J. J. (2013) · Hippocampus · doi:10.1002/hipo.22101 · Cited by 217 · see citing works
Cingulate cortex projections to the parahippocampal region and hippocampal formation in the rat
Jones, B. F., & Witter, M. P. (2007) · Hippocampus · doi:10.1002/hipo.20330 · Cited by 201 · see citing works
Distinct roles of medial and lateral entorhinal cortex in spatial cognition
Van Cauter, T., Camon, J., Alvernhe, A., Elduayen, C., Sargolini, F., & Save, E. (2013) · Cerebral Cortex · doi:10.1093/cercor/bhs033 · Cited by 196 · see citing works
Nitz, D. A., & McNaughton, B. L. (2004) · Journal of Neurophysiology · doi:10.1152/jn.00614.2003 · Cited by 184 · see citing works
VanElzakker, M. B., Fevurly, R. D., Breindel, T., & Spencer, R. L. (2008) · Learning & Memory · doi:10.1101/lm.1196508 · Cited by 179 · see citing works
Kleschevnikov, A. M., Belichenko, P. V., Faizi, M., Jacobs, L. F., Htun, K. E., Shamloo, M., & Mobley, W. C. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.1673-12.2012 · Cited by 174 · see citing works
Hippocampal Sharp Wave/Ripples during Sleep for Consolidation of Associative Memory
Ramadan, W., Eschenko, O., & Sara, S. J. (2009) · PLoS ONE · doi:10.1371/journal.pone.0006697 · Cited by 173 · see citing works
Zhang, R., Xue, G., Wang, S., Zhang, L., Shi, C., & Xie, X. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-120151 · Cited by 146 · see citing works
Csicsvari, J. L., O'Neill, J., Allen, K. L., & Senior, T. J. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2007.05684.x · Cited by 145 · see citing works
Neglected aspects of exploratory and investigatory behavior
Renner, M. (1990) · Psychobiology · doi:10.3758/bf03327209 · Cited by 142 · see citing works
Place Field Repetition and Purely Local Remapping in a Multicompartment Environment
Spiers, H. J., Hayman, R. M. A., Jovalekic, A., Marozzi, E., & Jeffery, K. J. (2015) · Cerebral Cortex · doi:10.1093/cercor/bht198 · Cited by 138 · see citing works
Lateral entorhinal cortex is necessary for associative but not nonassociative recognition memory
Wilson, D. I. G., Watanabe, S., Milner, H., & Ainge, J. A. (2013) · Hippocampus · doi:10.1002/hipo.22165 · Cited by 137 · see citing works
Aging impairs hippocampus-dependent long-term memory for object location in mice
Wimmer, M. E., Hernandez, P. J., Blackwell, J. M., & Abel, T. G. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.07.007 · Cited by 128 · see citing works
Rapid and Continuous Modulation of Hippocampal Network State during Exploration of New Places
Kemere, C. T., Carr, M. F., Karlsson, M. P., & Frank, L. M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0073114 · Cited by 122 · see citing works
Self-citationNeural Correlates of Long-Term Object Memory in the Mouse Anterior Cingulate Cortex
Weible, A. P., Rowland, D. C., Monaghan, C. K., Wolfgang, N. T., & Kentros, C. G. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.5265-11.2012 · Cited by 110 · see citing works
Object recognition memory and BDNF expression are reduced in young TgCRND8 mice
Francis, B. M., Kim, J., Barakat, M., Fraenkl, S. A., Yücel, Y. H., Peng, S., Michalski, B., Fahnestock, M. L., McLaurin, J., & Mount, H. T. J. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.04.003 · Cited by 108 · see citing works
Weible, A. P., Rowland, D. C., Pang, R. D., & Kentros, C. G. (2009) · Journal of Neurophysiology · doi:10.1152/jn.00214.2009 · Cited by 99 · see citing works
Lenck-Santini, P.-P., Rivard, B., Muller, R. U., & Poucet, B. (2005) · Hippocampus · doi:10.1002/hipo.20060 · Cited by 81 · see citing works
Singer, A. C., Karlsson, M. P., Nathe, A. R., Carr, M. F., & Frank, L. M. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.0926-10.2010 · Cited by 80 · see citing works
Self-citationMacrophage and microglia-like cells in the avian inner ear
Bhave, S. A., Oesterle, E. C., & Coltrera, M. D. (1998) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19980824)398:2 · Cited by 77 · see citing works
Gerstein, H., Hullinger, R., Lindstrom, M. J., & Bürger, C. (2013) · PLoS ONE · doi:10.1371/journal.pone.0062360 · Cited by 20 · see citing works
Frank, L. M., Kemere, C. T., Carr, M. K. V., et al. (2013) · Cited by 4 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Gillespie, A. K., Jones, E. A., Lin, Y.-H., Karlsson, M. P., Kay, K., Yoon, S. Y., Tong, L. M., Nova, P., Carr, J. S., Frank, L. M., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.04.009 · Cited by 187 · see citing works
Self-citationChao, O. Y., de Souza Silva, M. A., Yang, Y.-M., & Huston, J. P. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.04.007 · Cited by 158 · see citing works
Hippocampal reactivation extends for several hours following novel experience
Giri, B., Miyawaki, H., Mizuseki, K., Cheng, S., & Diba, K. (2019) · The Journal of Neuroscience · doi:10.1523/jneurosci.1950-18.2018 · Cited by 99 · see citing works
Fast gamma rhythms in the hippocampus promote encoding of novel object-place pairings
Zheng, C., Bieri, K. W., Hwaun, E., & Colgin, L. L. (2016) · eNeuro · doi:10.1523/eneuro.0001-16.2016 · Cited by 79 · see citing works
Hippocampal release of dopamine and norepinephrine encodes novel contextual information
Moreno‐Castilla, P., Pérez‐Ortega, R., Violante‐Soria, V., Balderas, I., & Bermúdez‐Rattoni, F. (2017) · Hippocampus · doi:10.1002/hipo.22711 · Cited by 67 · see citing works
Chao, O. Y., Nikolaus, S., Lira Brandão, M., Huston, J. P., & de Souza Silva, M. A. (2017) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2017.03.019 · Cited by 38 · see citing works
Subregion-specific proteomic signature in the hippocampus for recognition processes in adult mice
von Ziegler, L. M., Selevsek, N., Tweedie-Cullen, R. Y., Kremer, E., & Mansuy, I. M. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.02.079 · Cited by 23 · see citing works
- Authors
- Larkin, M. C., Lykken, C., Tye, L. D., Wickelgren, J. G., & Frank, L. M.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Frank, Loren M.
- Venue
- Hippocampus
- Publisher
- Wiley
- Published
- 2014-03-21
- Volume
- 24
- Issue
- 7
- Pages
- 773-783
- ISSN
- 1050-9631 (ISSN-L)
- 1098-1063
- PMC
- PMC4065199
- OpenAlex
- W2119298323
- Cited by
- 110
- References
- 52
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 8 · 2023: 12 · 2022: 7 · 2021: 8 · 2020: 8 · 2019: 9 · 2018: 6 · 2017: 9 · 2016: 10 · 2015: 6 · 2014: 6
- FWCI
- 5.76
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Hippocampus (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Mental Health (R01MH090188, RO1MH080283, F31093067)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- hippocampal CA1, CA3, place cells, sharp-wave ripples, memory replay, spatial exploration, hippocampal plasticity, memory integration, rats
- MeSH terms
- Action Potentials, Animals, Exploratory Behavior, Male, Rats, Long-Evans, Recognition, Psychology, Rats, CA1 Region, Hippocampal, CA3 Region, Hippocampal, Spatial Memory
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
