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.


Logo for

Science 292 (5525): 2337-2340

Copyright © 2001 by the American Association for the Advancement of Science

Requirement of ERK Activation for Visual Cortical Plasticity

Graziella Di Cristo,1* Nicoletta Berardi,23dagger Laura Cancedda,1 Tommaso Pizzorusso,12 Elena Putignano,1 Gian Michele Ratto,2 Lamberto Maffei12

Experience-dependent plasticity in the developing visual cortex depends on electrical activity and molecular signals involved in stabilization or removal of inputs. Extracellular signal-regulated kinase 1,2 (also called p42/44 mitogen-activated protein kinase) activation in the cortex is regulated by both factors. We show that two different inhibitors of the ERK pathway suppress the induction of two forms of long-term potentiation (LTP) in rat cortical slices and that their intracortical administration to monocularly deprived rats prevents the shift in ocular dominance towards the nondeprived eye. These results demonstrate that the ERK pathway is necessary for experience-dependent plasticity and for LTP of synaptic transmission in the developing visual cortex.

1 Scuola Normale Superiore, Piazza Cavalieri, 7 56126 Pisa, Italy.
2 Istituto Neurofisiologia CNR, via Moruzzi 1, 56100 Pisa, Italy.
3 Dipartimento di Psicologia, Università di Firenze, 50123 Firenze, Italy.
*   Present address: Department of Neurobiology, Cold Spring Harbor Laboratory, Post Office Box 100, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.

dagger    To whom correspondence should be addressed. E-mail: berardi{at}

Extracellular Signal-Regulated Kinase (ERK) Activity During Sleep Consolidates Cortical Plasticity In Vivo.
M. C. Dumoulin, S. J. Aton, A. J. Watson, L. Renouard, T. Coleman, and M. G. Frank (2013)
Cereb Cortex
   Abstract »    Full Text »    PDF »
Interaction Between {alpha}CaMKII and GluN2B Controls ERK-Dependent Plasticity.
F. El Gaamouch, A. Buisson, O. Moustie, M. Lemieux, S. Labrecque, B. Bontempi, P. De Koninck, and O. Nicole (2012)
J. Neurosci. 32, 10767-10779
   Abstract »    Full Text »    PDF »
Inhibition of Matrix Metalloproteinases Prevents the Potentiation of Nondeprived-Eye Responses after Monocular Deprivation in Juvenile Rats.
M. Spolidoro, E. Putignano, C. Munafo, L. Maffei, and T. Pizzorusso (2012)
Cereb Cortex 22, 725-734
   Abstract »    Full Text »    PDF »
The Synaptic Proteome during Development and Plasticity of the Mouse Visual Cortex.
M. Dahlhaus, K. Wan Li, R. C. van der Schors, M. H. Saiepour, P. van Nierop, J. A. Heimel, J. M. Hermans, M. Loos, A. B. Smit, and C. N. Levelt (2011)
Mol. Cell. Proteomics 10, M110.005413
   Abstract »    Full Text »    PDF »
Constitutively active H-ras accelerates multiple forms of plasticity in developing visual cortex.
M. Kaneko, C. E. Cheetham, Y.-S. Lee, A. J. Silva, M. P. Stryker, and K. Fox (2010)
PNAS 107, 19026-19031
   Abstract »    Full Text »    PDF »
Oligodendrocyte-Myelin Glycoprotein and Nogo Negatively Regulate Activity-Dependent Synaptic Plasticity.
S. J. Raiker, H. Lee, K. T. Baldwin, Y. Duan, P. Shrager, and R. J. Giger (2010)
J. Neurosci. 30, 12432-12445
   Abstract »    Full Text »    PDF »
Reducing Intracortical Inhibition in the Adult Visual Cortex Promotes Ocular Dominance Plasticity.
A. Harauzov, M. Spolidoro, G. DiCristo, R. De Pasquale, L. Cancedda, T. Pizzorusso, A. Viegi, N. Berardi, and L. Maffei (2010)
J. Neurosci. 30, 361-371
   Abstract »    Full Text »    PDF »
Tight control of MEK-ERK activation is essential in regulating proliferation, survival, and cytokine production of CD34+-derived neutrophil progenitors.
C. R. Geest, M. Buitenhuis, M. J. A. Groot Koerkamp, F. C. P. Holstege, E. Vellenga, and P. J. Coffer (2009)
Blood 114, 3402-3412
   Abstract »    Full Text »    PDF »
Molecular mechanisms of experience-dependent plasticity in visual cortex.
D. Tropea, A. Van Wart, and M. Sur (2009)
Phil Trans R Soc B 364, 341-355
   Abstract »    Full Text »    PDF »
Persistent ERK activation maintains learning-induced long-lasting modulation of synaptic connectivity.
S. I. Cohen-Matsliah, Y. Seroussi, K. Rosenblum, and E. Barkai (2008)
Learn. Mem. 15, 756-761
   Abstract »    Full Text »    PDF »
Activation of mitogen-activated protein kinase kinase (MEK)/extracellular signal regulated kinase (ERK) signaling pathway is involved in myeloid lineage commitment.
C.-L. Hsu, K. Kikuchi, and M. Kondo (2007)
Blood 110, 1420-1428
   Abstract »    Full Text »    PDF »
Retinal functional development is sensitive to environmental enrichment: a role for BDNF.
S. Landi, A. Sale, N. Berardi, A. Viegi, L. Maffei, and M. C. Cenni (2007)
FASEB J 21, 130-139
   Abstract »    Full Text »    PDF »
Muscarinic acetylcholine receptor knockout mice show distinct synaptic plasticity impairments in the visual cortex.
N. Origlia, N. Kuczewski, E. Aztiria, D. Gautam, J. Wess, and L. Domenici (2006)
J. Physiol. 577, 829-840
   Abstract »    Full Text »    PDF »
Long-Term Potentiation Is Mediated by Multiple Kinase Cascades Involving CaMKII or Either PKA or p42/44 MAPK in the Adult Rat Dentate Gyrus In Vitro.
J. Wu, M. J. Rowan, and R. Anwyl (2006)
J Neurophysiol 95, 3519-3527
   Abstract »    Full Text »    PDF »
Synaptic Ras GTPase Activating Protein Regulates Pattern Formation in the Trigeminal System of Mice.
M. W. Barnett, R. F. Watson, T. Vitalis, K. Porter, N. H. Komiyama, P. N. Stoney, T. H. Gillingwater, S. G. N. Grant, and P. C. Kind (2006)
J. Neurosci. 26, 1355-1365
   Abstract »    Full Text »    PDF »
Postnatal Expression Profile of OBCAM Implies its Involvement in Visual Cortex Development and Plasticity.
P. Li, S.S. Prasad, D.E. Mitchell, A. Hachisuka, J.-I. Sawada, A.M. Al-Housseini, and Q. Gu (2006)
Cereb Cortex 16, 291-299
   Abstract »    Full Text »    PDF »
Reversible intracellular translocation of KRas but not HRas in hippocampal neurons regulated by Ca2+/calmodulin.
M. Fivaz and T. Meyer (2005)
J. Cell Biol. 170, 429-441
   Abstract »    Full Text »    PDF »
A semi-persistent adult ocular dominance plasticity in visual cortex is stabilized by activated CREB.
T. A. Pham, S. J. Graham, S. Suzuki, A. Barco, E. R. Kandel, B. Gordon, and M. E. Lickey (2004)
Learn. Mem. 11, 738-747
   Abstract »    Full Text »    PDF »
Requirement for the RII{beta} Isoform of PKA, But Not Calcium-Stimulated Adenylyl Cyclase, in Visual Cortical Plasticity.
Q. S. Fischer, C. J. Beaver, Y. Yang, Y. Rao, K. B. Jakobsdottir, D. R. Storm, G. S. McKnight, and N. W. Daw (2004)
J. Neurosci. 24, 9049-9058
   Abstract »    Full Text »    PDF »
Recovery of Cortical Binocularity and Orientation Selectivity After the Critical Period for Ocular Dominance Plasticity.
D. S. Liao, T. E. Krahe, G. T. Prusky, A. E. Medina, and A. S. Ramoa (2004)
J Neurophysiol 92, 2113-2121
   Abstract »    Full Text »    PDF »
ERK signaling is required for eye-specific retino-geniculate segregation.
S. Naska, M. C. Cenni, E. Menna, and L. Maffei (2004)
Development 131, 3559-3570
   Abstract »    Full Text »    PDF »
Long-Term Potentiation and Memory.
M. A. LYNCH (2004)
Physiol Rev 84, 87-136
   Abstract »    Full Text »    PDF »
Neonatal Alcohol Exposure Induces Long-Lasting Impairment of Visual Cortical Plasticity in Ferrets.
A. E. Medina, T. E. Krahe, D. M. Coppola, and A. S. Ramoa (2003)
J. Neurosci. 23, 10002-10012
   Abstract »    Full Text »    PDF »
Patterned Vision Causes CRE-Mediated Gene Expression in the Visual Cortex through PKA and ERK.
L. Cancedda, E. Putignano, S. Impey, L. Maffei, G. M. Ratto, and T. Pizzorusso (2003)
J. Neurosci. 23, 7012-7020
   Abstract »    Full Text »    PDF »
Roles of Protein Kinase A and Protein Kinase G in Synaptic Plasticity in the Visual Cortex.
S. Liu, Y. Rao, and N. Daw (2003)
Cereb Cortex 13, 864-869
   Abstract »    Full Text »    PDF »
Cooperative Activation of Dopamine D1 and D2 Receptors Increases Spike Firing of Nucleus Accumbens Neurons via G-Protein {beta}{gamma} Subunits.
F. W. Hopf, M. G. Cascini, A. S. Gordon, I. Diamond, and A. Bonci (2003)
J. Neurosci. 23, 5079-5087
   Abstract »    Full Text »    PDF »
Dark Rearing Alters the Development of GABAergic Transmission in Visual Cortex.
B. Morales, S.-Y. Choi, and A. Kirkwood (2002)
J. Neurosci. 22, 8084-8090
   Abstract »    Full Text »    PDF »
Absence of Long-Term Depression in the Visual Cortex of Glutamic Acid Decarboxylase-65 Knock-Out Mice.
S.-Y. Choi, B. Morales, H.-K. Lee, and A. Kirkwood (2002)
J. Neurosci. 22, 5271-5276
   Abstract »    Full Text »    PDF »
Permissive proteolytic activity for visual cortical plasticity.
N. Mataga, N. Nagai, and T. K. Hensch (2002)
PNAS 99, 7717-7721
   Abstract »    Full Text »    PDF »
The Herpes Simplex Virus Type 2 R1 Protein Kinase (ICP10 PK) Blocks Apoptosis in Hippocampal Neurons, Involving Activation of the MEK/MAPK Survival Pathway.
D. Perkins, E. F. R. Pereira, M. Gober, P. J. Yarowsky, and L. Aurelian (2002)
J. Virol. 76, 1435-1449
   Abstract »    Full Text »    PDF »
Experience-dependent plasticity without long-term depression by type 2 metabotropic glutamate receptors in developing visual cortex.
J. J. Renger, K. N. Hartman, Y. Tsuchimoto, M. Yokoi, S. Nakanishi, and T. K. Hensch (2002)
PNAS 99, 1041-1046
   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