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 304 (5672): 881-883

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

The Involvement of the Anterior Cingulate Cortex in Remote Contextual Fear Memory

Paul W. Frankland,1,2,3* Bruno Bontempi,4* Lynn E. Talton,1 Leszek Kaczmarek,1,5 Alcino J. Silva1{dagger}

Abstract: Although the molecular, cellular, and systems mechanisms required for initial memory processing have been intensively investigated, those underlying permanent memory storage remain elusive. We present neuroanatomical, pharmacological, and genetic results demonstrating that the anterior cingulate cortex plays a critical role in remote memory for contextual fear conditioning. Imaging of activity-dependent genes shows that the anterior cingulate is activated by remote memory and that this activation is impaired by a null {alpha}-CaMKII mutation that blocks remote memory. Accordingly, reversible inactivation of this structure in normal mice disrupts remote memory without affecting recent memory.

1 Departments of Neurobiology, Psychiatry, Psychology and Brain Research Institute, UCLA, 695 Charles Young Drive South, Los Angeles, CA 90095–1761, USA.
2 Department of Integrative Biology, Hospital for Sick Children Research Institute, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8.
3 Department of Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8.
4 Laboratoire de Neurosciences Cognitives, CNRS UMR 5106, Avenue des Facultés, 33405 Talence, France.
5 Nencki Institute, Pasteura 3, 02–093, Warsaw, Poland.

Back to Top

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: silvaa{at}mednet.ucla.edu.

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Hippocampus and medial prefrontal cortex contributions to trace and contextual fear memory expression over time.
C. L. Beeman, P. S. Bauer, J. L. Pierson, and J. J. Quinn (2013)
Learn. Mem. 20, 336-343
   Abstract »    Full Text »    PDF »
Portraying the unique contribution of the default mode network to internally driven mnemonic processes.
I. Shapira-Lichter, N. Oren, Y. Jacob, M. Gruberger, and T. Hendler (2013)
PNAS 110, 4950-4955
   Abstract »    Full Text »    PDF »
Functional integrity of the retrosplenial cortex is essential for rapid consolidation and recall of fear memory.
C. Katche, G. Dorman, L. Slipczuk, M. Cammarota, and J. H. Medina (2013)
Learn. Mem. 20, 170-173
   Abstract »    Full Text »    PDF »
Epigenetic regulation of memory formation and maintenance.
I. B. Zovkic, M. C. Guzman-Karlsson, and J. D. Sweatt (2013)
Learn. Mem. 20, 61-74
   Abstract »    Full Text »    PDF »
The episodic engram transformed: Time reduces retrieval-related brain activity but correlates it with memory accuracy.
O. Furman, A. Mendelsohn, and Y. Dudai (2012)
Learn. Mem. 19, 575-587
   Abstract »    Full Text »    PDF »
Kainate receptor-mediated synaptic transmissions in the adult rodent insular cortex.
K. Koga, S.-E. Sim, T. Chen, L.-J. Wu, B.-K. Kaang, and M. Zhuo (2012)
J Neurophysiol 108, 1988-1998
   Abstract »    Full Text »    PDF »
Involvement of the anterior cingulate cortex in formation, consolidation, and reconsolidation of recent and remote contextual fear memory.
E. O. Einarsson and K. Nader (2012)
Learn. Mem. 19, 449-452
   Abstract »    Full Text »    PDF »
New approaches to neural circuits in behavior.
A. Garner and M. Mayford (2012)
Learn. Mem. 19, 385-390
   Abstract »    Full Text »    PDF »
Infantile amnesia: A neurogenic hypothesis.
S. A. Josselyn and P. W. Frankland (2012)
Learn. Mem. 19, 423-433
   Abstract »    Full Text »    PDF »
The Ventral Midline Thalamus (Reuniens and Rhomboid Nuclei) Contributes to the Persistence of Spatial Memory in Rats.
M. Loureiro, T. Cholvin, J. Lopez, N. Merienne, A. Latreche, B. Cosquer, K. Geiger, C. Kelche, J.-C. Cassel, and A. Pereira de Vasconcelos (2012)
J. Neurosci. 32, 9947-9959
   Abstract »    Full Text »    PDF »
Neural Correlates of Long-Term Object Memory in the Mouse Anterior Cingulate Cortex.
A. P. Weible, D. C. Rowland, C. K. Monaghan, N. T. Wolfgang, and C. G. Kentros (2012)
J. Neurosci. 32, 5598-5608
   Abstract »    Full Text »    PDF »
Extinction partially reverts structural changes associated with remote fear memory.
G. Vetere, L. Restivo, G. Novembre, M. Aceti, M. Lumaca, and M. Ammassari-Teule (2011)
Learn. Mem. 18, 554-557
   Abstract »    Full Text »    PDF »
NMDA Receptors in Retrosplenial Cortex Are Necessary for Retrieval of Recent and Remote Context Fear Memory.
K. A. Corcoran, M. D. Donnan, N. C. Tronson, Y. F. Guzman, C. Gao, V. Jovasevic, A. L. Guedea, and J. Radulovic (2011)
J. Neurosci. 31, 11655-11659
   Abstract »    Full Text »    PDF »
Spine growth in the anterior cingulate cortex is necessary for the consolidation of contextual fear memory.
G. Vetere, L. Restivo, C. J. Cole, P. J. Ross, M. Ammassari-Teule, S. A. Josselyn, and P. W. Frankland (2011)
PNAS 108, 8456-8460
   Abstract »    Full Text »    PDF »
Bidirectional control of BK channel open probability by CAMKII and PKC in medial vestibular nucleus neurons.
I. van Welie and S. du Lac (2011)
J Neurophysiol 105, 1651-1659
   Abstract »    Full Text »    PDF »
Repeatedly reactivated memories become more resistant to hippocampal damage.
H. Lehmann and K. C. McNamara (2011)
Learn. Mem. 18, 132-135
   Abstract »    Full Text »    PDF »
Role of Secondary Sensory Cortices in Emotional Memory Storage and Retrieval in Rats.
T. Sacco and B. Sacchetti (2010)
Science 329, 649-656
   Abstract »    Full Text »    PDF »
Trace and contextual fear conditioning require neural activity and NMDA receptor-dependent transmission in the medial prefrontal cortex.
M. R. Gilmartin and F. J. Helmstetter (2010)
Learn. Mem. 17, 289-296
   Abstract »    Full Text »    PDF »
Engagement of the PFC in consolidation and recall of recent spatial memory.
W. C. Leon, M. A. Bruno, S. Allard, K. Nader, and A. C. Cuello (2010)
Learn. Mem. 17, 297-305
   Abstract »    Full Text »    PDF »
Dissociation of within- and between-Session Extinction of Conditioned Fear.
W. Plendl and C. T. Wotjak (2010)
J. Neurosci. 30, 4990-4998
   Abstract »    Full Text »    PDF »
Plastic Synaptic Networks of the Amygdala for the Acquisition, Expression, and Extinction of Conditioned Fear.
H. C. Pape and D. Pare (2010)
Physiol Rev 90, 419-463
   Abstract »    Full Text »    PDF »
The Medial Prefrontal Cortex and Integration in Autism.
D. B. Shalom (2009)
Neuroscientist 15, 589-598
   Abstract »    PDF »
Hyperdopaminergic Tone Erodes Prefrontal Long-Term Potential via a D2 Receptor-Operated Protein Phosphatase Gate.
T.-X. Xu, T. D. Sotnikova, C. Liang, J. Zhang, J. U. Jung, R. D. Spealman, R. R. Gainetdinov, and W.-D. Yao (2009)
J. Neurosci. 29, 14086-14099
   Abstract »    Full Text »    PDF »
Changes in context-specificity during memory reconsolidation: Selective effects of hippocampal lesions.
G. Winocur, P. W. Frankland, M. Sekeres, S. Fogel, and M. Moscovitch (2009)
Learn. Mem. 16, 722-729
   Abstract »    Full Text »    PDF »
Neural Correlates of Novel Object and Novel Location Recognition Behavior in the Mouse Anterior Cingulate Cortex.
A. P. Weible, D. C. Rowland, R. Pang, and C. Kentros (2009)
J Neurophysiol 102, 2055-2068
   Abstract »    Full Text »    PDF »
Sleep deprivation and Pavlovian fear conditioning.
D. J. Cai, T. Shuman, E. M. Harrison, J. R. Sage, and S. G. Anagnostaras (2009)
Learn. Mem. 16, 595-599
   Abstract »    Full Text »    PDF »
Remote spatial memory and the hippocampus: Effect of early and extensive training in the radial maze.
J. M.J. Ramos (2009)
Learn. Mem. 16, 554-563
   Abstract »    Full Text »    PDF »
Persistence of fear memory across time requires the basolateral amygdala complex.
A. M. Poulos, V. Li, S. S. Sterlace, F. Tokushige, R. Ponnusamy, and M. S. Fanselow (2009)
PNAS 106, 11737-11741
   Abstract »    Full Text »    PDF »
Ca2+/Calmodulin-dependent Protein Kinase IV Links Group I Metabotropic Glutamate Receptors to Fragile X Mental Retardation Protein in Cingulate Cortex.
H. Wang, H. Fukushima, S. Kida, and M. Zhuo (2009)
J. Biol. Chem. 284, 18953-18962
   Abstract »    Full Text »    PDF »
Selective Cortical Layering Abnormalities and Behavioral Deficits in Cortex-Specific Pax6 Knock-Out Mice.
T. C. Tuoc, K. Radyushkin, A. B. Tonchev, M. C. Pinon, R. Ashery-Padan, Z. Molnar, M. S. Davidoff, and A. Stoykova (2009)
J. Neurosci. 29, 8335-8349
   Abstract »    Full Text »    PDF »
The Formation of Recent and Remote Memory Is Associated with Time-Dependent Formation of Dendritic Spines in the Hippocampus and Anterior Cingulate Cortex.
L. Restivo, G. Vetere, B. Bontempi, and M. Ammassari-Teule (2009)
J. Neurosci. 29, 8206-8214
   Abstract »    Full Text »    PDF »
New hippocampal neurons are not obligatory for memory formation; cyclin D2 knockout mice with no adult brain neurogenesis show learning.
P. Jaholkowski, A. Kiryk, P. Jedynak, N. M. Ben Abdallah, E. Knapska, A. Kowalczyk, A. Piechal, K. Blecharz-Klin, I. Figiel, V. Lioudyno, et al. (2009)
Learn. Mem. 16, 439-451
   Abstract »    Full Text »    PDF »
The Intralaminar Thalamic Nuclei Contribute to Remote Spatial Memory.
J. Lopez, M. Wolff, L. Lecourtier, B. Cosquer, B. Bontempi, J. Dalrymple-Alford, and J.-C. Cassel (2009)
J. Neurosci. 29, 3302-3306
   Abstract »    Full Text »    PDF »
Medial Temporal Lobe Activity during Retrieval of Semantic Memory Is Related to the Age of the Memory.
C. N. Smith and L. R. Squire (2009)
J. Neurosci. 29, 930-938
   Abstract »    Full Text »    PDF »
Brain Region-Specific Gene Expression Activation Required for Reconsolidation and Extinction of Contextual Fear Memory.
N. Mamiya, H. Fukushima, A. Suzuki, Z. Matsuyama, S. Homma, P. W. Frankland, and S. Kida (2009)
J. Neurosci. 29, 402-413
   Abstract »    Full Text »    PDF »
Coupling of Theta Oscillations between Anterior and Posterior Midline Cortex and with the Hippocampus in Freely Behaving Rats.
C. K. Young and N. McNaughton (2009)
Cereb Cortex 19, 24-40
   Abstract »    Full Text »    PDF »
The NMDA Agonist D-Cycloserine Facilitates Fear Memory Consolidation in Humans.
R. Kalisch, B. Holt, P. Petrovic, B. De Martino, S. Kloppel, C. Buchel, and R. J. Dolan (2009)
Cereb Cortex 19, 187-196
   Abstract »    Full Text »    PDF »
Type 1 Adenylyl Cyclase Is Essential for Maintenance of Remote Contextual Fear Memory.
Q. Shan, G. C.-K. Chan, and D. R. Storm (2008)
J. Neurosci. 28, 12864-12867
   Abstract »    Full Text »    PDF »
Spontaneous Changes of Neocortical Code for Associative Memory During Consolidation.
K. Takehara-Nishiuchi and B. L. McNaughton (2008)
Science 322, 960-963
   Abstract »    Full Text »    PDF »
Theta synchronizes the activity of medial prefrontal neurons during learning.
R. Paz, E. P. Bauer, and D. Pare (2008)
Learn. Mem. 15, 524-531
   Abstract »    Full Text »    PDF »
Inactivation of the anterior cingulate cortex blocks expression of remote, but not recent, conditioned taste aversion memory.
H. K. Ding, C. M. Teixeira, and P. W. Frankland (2008)
Learn. Mem. 15, 290-293
   Abstract »    Full Text »    PDF »
Inverse temporal contributions of the dorsal hippocampus and medial prefrontal cortex to the expression of long-term fear memories.
J. J. Quinn, Q. D. Ma, M. R. Tinsley, C. Koch, and M. S. Fanselow (2008)
Learn. Mem. 15, 368-372
   Abstract »    Full Text »    PDF »
Roles of Calcium-Stimulated Adenylyl Cyclase and Calmodulin-Dependent Protein Kinase IV in the Regulation of FMRP by Group I Metabotropic Glutamate Receptors.
H. Wang, L.-J. Wu, F. Zhang, and M. Zhuo (2008)
J. Neurosci. 28, 4385-4397
   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 »
Fast-Forward Playback of Recent Memory Sequences in Prefrontal Cortex During Sleep.
D. R. Euston, M. Tatsuno, and B. L. McNaughton (2007)
Science 318, 1147-1150
   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 »
Functional Internal Complexity of Amygdala: Focus on Gene Activity Mapping After Behavioral Training and Drugs of Abuse.
E. Knapska, K. Radwanska, T. Werka, and L. Kaczmarek (2007)
Physiol Rev 87, 1113-1173
   Abstract »    Full Text »    PDF »
Reorganization of learning-associated prefrontal synaptic plasticity between the recall of recent and remote fear extinction memory.
S. Hugues and R. Garcia (2007)
Learn. Mem. 14, 520-524
   Abstract »    Full Text »    PDF »
Memory trace stabilization leads to large-scale changes in the retrieval network: A functional MRI study on associative memory.
A. Takashima, I. L.C. Nieuwenhuis, M. Rijpkema, K. M. Petersson, O. Jensen, and G. Fernandez (2007)
Learn. Mem. 14, 472-479
   Abstract »    Full Text »    PDF »
Learning-Related Facilitation of Rhinal Interactions by Medial Prefrontal Inputs.
R. Paz, E. P. Bauer, and D. Pare (2007)
J. Neurosci. 27, 6542-6551
   Abstract »    Full Text »    PDF »
Alteration of cingulate long-term plasticity and behavioral sensitization to inflammation by environmental enrichment.
F. W.F. Shum, L.-J. Wu, M.-G. Zhao, H. Toyoda, H. Xu, M. Ren, R. Pinaud, S. W. Ko, Y.-S. Lee, B.-K. Kaang, et al. (2007)
Learn. Mem. 14, 304-312
   Abstract »    Full Text »    PDF »
Memory for context becomes less specific with time.
B. J. Wiltgen and A. J. Silva (2007)
Learn. Mem. 14, 313-317
   Abstract »    Full Text »    PDF »
Context preexposure prevents forgetting of a contextual fear memory: Implication for regional changes in brain activation patterns associated with recent and remote memory tests.
J. C. Biedenkapp and J. W. Rudy (2007)
Learn. Mem. 14, 200-203
   Abstract »    Full Text »    PDF »
Lost forever or temporarily misplaced? The long debate about the nature of memory impairment..
L. R. Squire (2006)
Learn. Mem. 13, 522-529
   Abstract »    Full Text »    PDF »
Dynamic neuroplasticity and the automation of motivated behavior..
B. J. Aragona and R. M. Carelli (2006)
Learn. Mem. 13, 558-559
   Full Text »    PDF »
Enhanced Presynaptic Neurotransmitter Release in the Anterior Cingulate Cortex of Mice with Chronic Pain..
M.-G. Zhao, S. W Ko, L.-J. Wu, H. Toyoda, H. Xu, J. Quan, J. Li, Y. Jia, M. Ren, Z. C. Xu, et al. (2006)
J. Neurosci. 26, 8923-8930
   Abstract »    Full Text »    PDF »
Involvement of the anterior cingulate cortex in the expression of remote spatial memory..
C. M. Teixeira, S. R. Pomedli, H. R. Maei, N. Kee, and P. W. Frankland (2006)
J. Neurosci. 26, 7555-7564
   Abstract »    Full Text »    PDF »
Stability of recent and remote contextual fear memory.
P. W. Frankland, H.-K. Ding, E. Takahashi, A. Suzuki, S. Kida, and A. J. Silva (2006)
Learn. Mem. 13, 451-457
   Abstract »    Full Text »    PDF »
Systems Consolidation Requires Postlearning Activation of NMDA Receptors in the Medial Prefrontal Cortex in Trace Eyeblink Conditioning..
K. Takehara-Nishiuchi, K. Nakao, S. Kawahara, N. Matsuki, and Y. Kirino (2006)
J. Neurosci. 26, 5049-5058
   Abstract »    Full Text »    PDF »
Dynamics of hippocampal and cortical activation during consolidation of a nonspatial memory..
R. S. Ross and H. Eichenbaum (2006)
J. Neurosci. 26, 4852-4859
   Abstract »    Full Text »    PDF »
Place learning in the Morris water task: Making the memory stick.
K. Bolding and J. W. Rudy (2006)
Learn. Mem. 13, 278-286
   Abstract »    Full Text »    PDF »
Fast track to the medial prefrontal cortex.
P. W. Frankland and B. Bontempi (2006)
PNAS 103, 509-510
   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 »
Prefrontal cortex and the organization of recent and remote memories: An alternative view.
J. W. Rudy, J. C. Biedenkapp, and R. C. O'Reilly (2005)
Learn. Mem. 12, 445-446
   Full Text »    PDF »
Deficits in Trace Fear Memory and Long-Term Potentiation in a Mouse Model for Fragile X Syndrome.
M.-G. Zhao, H. Toyoda, S. W. Ko, H.-K. Ding, L.-J. Wu, and M. Zhuo (2005)
J. Neurosci. 25, 7385-7392
   Abstract »    Full Text »    PDF »
Neuronal Leucine-Rich Repeat Protein 4 Functions in Hippocampus-Dependent Long-Lasting Memory.
T. Bando, K. Sekine, S. Kobayashi, A. M. Watabe, A. Rump, M. Tanaka, Y. Suda, S. Kato, Y. Morikawa, T. Manabe, et al. (2005)
Mol. Cell. Biol. 25, 4166-4175
   Abstract »    Full Text »    PDF »
Mapping neuronal activation and the influence of adrenergic signaling during contextual memory retrieval.
W.-P. Zhang, J. F. Guzowski, and S. A. Thomas (2005)
Learn. Mem. 12, 239-247
   Abstract »    Full Text »    PDF »
Mouse Genetic Approaches to Investigating Calcium/Calmodulin-Dependent Protein Kinase II Function in Plasticity and Cognition.
Y. Elgersma, J. D. Sweatt, and K. P. Giese (2004)
J. Neurosci. 24, 8410-8415
   Full Text »    PDF »
Sites of Neocortical Reorganization Critical for Remote Spatial Memory.
T. Maviel, T. P. Durkin, F. Menzaghi, and B. Bontempi (2004)
Science 305, 96-99
   Abstract »    Full Text »    PDF »
NEUROSCIENCE: Zif and the Survival of Memory.
I.án Izquierdo and M.ín Cammarota (2004)
Science 304, 829-830
   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