 |
 Previous Article | Next Article 
The Journal of Neuroscience, May 1, 1999, 19(9):3535-3544
A Mitogen-Activated Protein Kinase Cascade in the CA1/CA2
Subfield of the Dorsal Hippocampus Is Essential for Long-Term Spatial
Memory
Sonja
Blum,
Anthony N.
Moore,
Frank
Adams, and
Pramod
K.
Dash
Department of Neurobiology and Anatomy, W. M. Keck Center for
the Neurobiology of Learning and Memory, The University of Texas
Medical School, Houston, Texas 77030
Behavioral, biophysical, and pharmacological studies have
implicated the hippocampus in the formation and storage of spatial memory. However, the molecular mechanisms underlying long-term spatial
memory are poorly understood. In this study, we show that mitogen-activated protein kinase (MAPK, also called ERK) is activated in the dorsal, but not the ventral, hippocampus of rats after training
in a spatial memory task, the Morris water maze. The activation was
expressed as enhanced phosphorylation of MAPK in the pyramidal neurons
of the CA1/CA2 subfield. In contrast, no increase in the percentage of
phospho-MAPK-positive cells was detected in either the CA3 subfield or
the dentate gyrus. The enhanced phosphorylation was observed only after
multiple training trials but not after a single trial or after multiple
trials in which the location of the target platform was randomly
changed between each trial. Inhibition of the MAPK/ERK cascade in
dorsal hippocampi did not impair acquisition, but blocked the formation of long-term spatial memory. In contrast, intrahippocampal infusion of
SB203580, a specific inhibitor of the stress-activated MAPK (p38 MAPK),
did not interfere with memory storage. These results demonstrate a
MAPK-mediated cellular event in the CA1/CA2 subfields of the dorsal
hippocampus that is critical for long-term spatial memory.
Key words:
MAPK; hippocampus; Morris water maze; long-term memory; PD098059; p38MAPK
Copyright © 1999 Society for Neuroscience 0270-6474/99/1993535-10$05.00/0
This article has been cited by other articles:
|
|
|
|
 
S. I. Cohen-Matsliah, Y. Seroussi, K. Rosenblum, and E. Barkai
Persistent ERK activation maintains learning-induced long-lasting modulation of synaptic connectivity
Learn. Mem.,
October 2, 2008;
15(10):
756 - 761.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. M. Fernandez, M. C. Lewis, A. S. Pechenino, L. L. Harburger, P. T. Orr, J. E. Gresack, G. E. Schafe, and K. M. Frick
Estradiol-Induced Enhancement of Object Memory Consolidation Involves Hippocampal Extracellular Signal-Regulated Kinase Activation and Membrane-Bound Estrogen Receptors
J. Neurosci.,
August 27, 2008;
28(35):
8660 - 8667.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Ryu, K. Futai, M. Feliu, R. Weinberg, and M. Sheng
Constitutively Active Rap2 Transgenic Mice Display Fewer Dendritic Spines, Reduced Extracellular Signal-Regulated Kinase Signaling, Enhanced Long-Term Depression, and Impaired Spatial Learning and Fear Extinction
J. Neurosci.,
August 13, 2008;
28(33):
8178 - 8188.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. P. Kelly, Y.-F. Cheung, C. Favilla, S. J. Siegel, S. J. Kanes, M. D. Houslay, and T. Abel
Constitutive activation of the G-protein subunit G{alpha}s within forebrain neurons causes PKA-dependent alterations in fear conditioning and cortical Arc mRNA expression
Learn. Mem.,
January 28, 2008;
15(2):
75 - 83.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. I. Cohen-Matsliah, I. Brosh, K. Rosenblum, and E. Barkai
A Novel Role for Extracellular Signal-Regulated Kinase in Maintaining Long-Term Memory-Relevant Excitability Changes
J. Neurosci.,
November 14, 2007;
27(46):
12584 - 12589.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. B. Chwang, J. S. Arthur, A. Schumacher, and J. D. Sweatt
The Nuclear Kinase Mitogen- and Stress-Activated Protein Kinase 1 Regulates Hippocampal Chromatin Remodeling in Memory Formation
J. Neurosci.,
November 14, 2007;
27(46):
12732 - 12742.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Satoh, S. Endo, T. Ikeda, K. Yamada, M. Ito, M. Kuroki, T. Hiramoto, O. Imamura, Y. Kobayashi, Y. Watanabe, et al.
Extracellular Signal-Regulated Kinase 2 (ERK2) Knockdown Mice Show Deficits in Long-Term Memory; ERK2 Has a Specific Function in Learning and Memory
J. Neurosci.,
October 3, 2007;
27(40):
10765 - 10776.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Chen, Y. Miyamoto, K. Furuya, N. Mori, and M. Sokabe
PREGS Induces LTP in the Hippocampal Dentate Gyrus of Adult Rats Via the Tyrosine Phosphorylation International Cooperative Research CREB Signaling
J Neurophysiol,
September 1, 2007;
98(3):
1538 - 1548.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Nagai, K. Takuma, H. Kamei, Y. Ito, N. Nakamichi, D. Ibi, Y. Nakanishi, M. Murai, H. Mizoguchi, T. Nabeshima, et al.
Dopamine D1 receptors regulate protein synthesis-dependent long-term recognition memory via extracellular signal-regulated kinase 1/2 in the prefrontal cortex
Learn. Mem.,
March 2, 2007;
14(3):
117 - 125.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C.-H. Yang, C.-C. Huang, and K.-S. Hsu
Novelty exploration elicits a reversal of acute stress-induced modulation of hippocampal synaptic plasticity in the rat
J. Physiol.,
December 1, 2006;
577(2):
601 - 615.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Fodale, D. Quattrone, C. Trecroci, V. Caminiti, and L. B. Santamaria
Alzheimer's disease and anaesthesia: implications for the central cholinergic system
Br. J. Anaesth.,
October 1, 2006;
97(4):
445 - 452.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. A. Miller and J. D. Sweatt
Amnesia or retrieval deficit? Implications of a molecular approach to the question of reconsolidation.
Learn. Mem.,
September 1, 2006;
13(5):
498 - 505.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. K. Dash, S. A. Orsi, and A. N. Moore
Spatial Memory Formation and Memory-Enhancing Effect of Glucose Involves Activation of the Tuberous Sclerosis Complex-Mammalian Target of Rapamycin Pathway
J. Neurosci.,
August 2, 2006;
26(31):
8048 - 8056.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. F. Cooke and T. V. P. Bliss
Plasticity in the human central nervous system
Brain,
July 1, 2006;
129(7):
1659 - 1673.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Trifilieff, C. Herry, P. Vanhoutte, J. Caboche, A. Desmedt, G. Riedel, N. Mons, and J. Micheau
Foreground contextual fear memory consolidation requires two independent phases of hippocampal ERK/CREB activation
Learn. Mem.,
May 1, 2006;
13(3):
349 - 358.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Rumbaugh, J. P. Adams, J. H. Kim, and R. L. Huganir
Inaugural Article: SynGAP regulates synaptic strength and mitogen-activated protein kinases in cultured neurons
PNAS,
March 21, 2006;
103(12):
4344 - 4351.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Moosmang, N. Haider, N. Klugbauer, H. Adelsberger, N. Langwieser, J. Muller, M. Stiess, E. Marais, V. Schulla, L. Lacinova, et al.
Role of Hippocampal Cav1.2 Ca2+ Channels in NMDA Receptor-Independent Synaptic Plasticity and Spatial Memory
J. Neurosci.,
October 26, 2005;
25(43):
9883 - 9892.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Chin, J. J. Palop, J. Puolivali, C. Massaro, N. Bien-Ly, H. Gerstein, K. Scearce-Levie, E. Masliah, and L. Mucke
Fyn Kinase Induces Synaptic and Cognitive Impairments in a Transgenic Mouse Model of Alzheimer's Disease
J. Neurosci.,
October 19, 2005;
25(42):
9694 - 9703.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Alvarez-Jaimes, M. Feliciano-Rivera, M. Centeno-Gonzalez, and C. S. Maldonado-Vlaar
Contributions of the Mitogen-Activated Protein Kinase and Protein Kinase C Cascades in Spatial Learning and Memory Mediated by the Nucleus Accumbens
J. Pharmacol. Exp. Ther.,
September 1, 2005;
314(3):
1144 - 1157.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Zhao, J. P. Adams, and S. M. Dudek
Pattern-Dependent Role of NMDA Receptors in Action Potential Generation: Consequences on Extracellular Signal-Regulated Kinase Activation
J. Neurosci.,
July 27, 2005;
25(30):
7032 - 7039.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Sui, W. L. Anderson, and M. E. Gilbert
Impairment in Short-Term but Enhanced Long-Term Synaptic Potentiation and ERK Activation in Adult Hippocampal Area CA1 Following Developmental Thyroid Hormone Insufficiency*
Toxicol. Sci.,
May 1, 2005;
85(1):
647 - 656.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C.-H. Yang, C.-C. Huang, and K.-S. Hsu
Behavioral Stress Modifies Hippocampal Synaptic Plasticity through Corticosterone-Induced Sustained Extracellular Signal-Regulated Kinase/Mitogen-Activated Protein Kinase Activation
J. Neurosci.,
December 8, 2004;
24(49):
11029 - 11034.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. E. Hebert and P. K. Dash
Plasticity in the Entorhinal Cortex Suppresses Memory for Contextual Fear
J. Neurosci.,
November 10, 2004;
24(45):
10111 - 10116.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Levenson, K. J. O'Riordan, K. D. Brown, M. A. Trinh, D. L. Molfese, and J. D. Sweatt
Regulation of Histone Acetylation during Memory Formation in the Hippocampus
J. Biol. Chem.,
September 24, 2004;
279(39):
40545 - 40559.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Hugues, O. Deschaux, and R. Garcia
Postextinction Infusion of a Mitogen-Activated Protein Kinase Inhibitor Into the Medial Prefrontal Cortex Impairs Memory of the Extinction of Conditioned Fear
Learn. Mem.,
September 1, 2004;
11(5):
540 - 543.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H.-Y. Cheng and D. F. Clayton
Activation and Habituation of Extracellular Signal-Regulated Kinase Phosphorylation in Zebra Finch Auditory Forebrain during Song Presentation
J. Neurosci.,
August 25, 2004;
24(34):
7503 - 7513.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Peila, B. L. Rodriguez, L. R. White, and L. J. Launer
Fasting insulin and incident dementia in an elderly population of Japanese-American men
Neurology,
July 27, 2004;
63(2):
228 - 233.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Blum and P. K. Dash
A Cell-Permeable Phospholipase C{gamma}1-Binding Peptide Transduces Neurons and Impairs Long-Term Spatial Memory
Learn. Mem.,
May 1, 2004;
11(3):
239 - 243.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Mizoguchi, K. Yamada, M. Mizuno, T. Mizuno, A. Nitta, Y. Noda, and T. Nabeshima
Regulations of Methamphetamine Reward by Extracellular Signal-Regulated Kinase 1/2/ets-Like Gene-1 Signaling Pathway via the Activation of Dopamine Receptors
Mol. Pharmacol.,
May 1, 2004;
65(5):
1293 - 1301.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
J. D. Runyan, A. N. Moore, and P. K. Dash
A Role for Prefrontal Cortex in Memory Storage for Trace Fear Conditioning
J. Neurosci.,
February 11, 2004;
24(6):
1288 - 1295.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Crosio, E. Heitz, C. D. Allis, E. Borrelli, and P. Sassone-Corsi
Chromatin remodeling and neuronal response: multiple signaling pathways induce specific histone H3 modifications and early gene expression in hippocampal neurons
J. Cell Sci.,
December 15, 2003;
116(24):
4905 - 4914.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. R. Gerfen
D1 Dopamine Receptor Supersensitivity in the Dopamine-Depleted Striatum Animal Model of Parkinson's Disease
Neuroscientist,
December 1, 2003;
9(6):
455 - 462.
[Abstract]
[PDF]
|
|
|
|
|
|
|
M. Peters, K. Mizuno, L. Ris, M. Angelo, E. Godaux, and K. P. Giese
Loss of Ca2+/Calmodulin Kinase Kinase {beta} Affects the Formation of Some, But Not All, Types of Hippocampus-Dependent Long-Term Memory
J. Neurosci.,
October 29, 2003;
23(30):
9752 - 9760.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H.-Y. Wang, W. Li, N. J. Benedetti, and D. H. S. Lee
{alpha}7 Nicotinic Acetylcholine Receptors Mediate {beta}-Amyloid Peptide-induced Tau Protein Phosphorylation
J. Biol. Chem.,
August 22, 2003;
278(34):
31547 - 31553.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Kelly, S. Laroche, and S. Davis
Activation of Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase in Hippocampal Circuitry Is Required for Consolidation and Reconsolidation of Recognition Memory
J. Neurosci.,
June 15, 2003;
23(12):
5354 - 5360.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W.-L. Chien, K.-C. Liang, C.-M. Teng, S.-C. Kuo, F.-Y. Lee, and W.-M. Fu
Enhancement of Long-Term Potentiation by a Potent Nitric Oxide-Guanylyl Cyclase Activator, 3-(5-Hydroxymethyl-2-furyl)-1-benzyl-indazole
Mol. Pharmacol.,
June 1, 2003;
63(6):
1322 - 1328.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-M. Park, T. Kunieda, and T. Kubo
The Activity of Mblk-1, a Mushroom Body-selective Transcription Factor from the Honeybee, Is Modulated by the Ras/MAPK Pathway
J. Biol. Chem.,
May 9, 2003;
278(20):
18689 - 18694.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. K. Sharma, C. M. Sherff, J. Shobe, M. W. Bagnall, M. A. Sutton, and T. J. Carew
Differential Role of Mitogen-Activated Protein Kinase in Three Distinct Phases of Memory for Sensitization in Aplysia
J. Neurosci.,
May 1, 2003;
23(9):
3899 - 3907.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Dhaka, R. M. Costa, H. Hu, D. K. Irvin, A. Patel, H. I. Kornblum, A. J. Silva, T. J. O'Dell, and J. Colicelli
The RAS Effector RIN1 Modulates the Formation of Aversive Memories
J. Neurosci.,
February 1, 2003;
23(3):
748 - 757.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. L. Berkeley and A. I. Levey
Cell-Specific Extracellular Signal-Regulated Kinase Activation by Multiple G Protein-Coupled Receptor Families in Hippocampus
Mol. Pharmacol.,
January 1, 2003;
63(1):
128 - 135.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A Hanauer and I D Young
Coffin-Lowry syndrome: clinical and molecular features
J. Med. Genet.,
October 1, 2002;
39(10):
705 - 713.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Q. Butcher, H. Dziema, M. Collamore, P. W. Burgoon, and K. Obrietan
The p42/44 Mitogen-activated Protein Kinase Pathway Couples Photic Input to Circadian Clock Entrainment
J. Biol. Chem.,
August 9, 2002;
277(33):
29519 - 29525.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. T. Dineley, K. A. Bell, D. Bui, and J. D. Sweatt
beta -Amyloid Peptide Activates alpha 7 Nicotinic Acetylcholine Receptors Expressed in Xenopus Oocytes
J. Biol. Chem.,
July 5, 2002;
277(28):
25056 - 25061.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Reisberg, E. H. Franssen, L. E.M. Souren, S. R. Auer, I. Akram, and S. Kenowsky
Evidence and mechanisms of retrogenesis in Alzheimer's and other dementias: Management and treatment import
American Journal of Alzheimer's Disease and Other Dementias,
July 1, 2002;
17(4):
202 - 212.
[Abstract]
[PDF]
|
|
|
|
|
|
|
A. E. Hebert and P. K. Dash
Extracellular Signal-Regulated Kinase Activity in the Entorhinal Cortex Is Necessary for Long-Term Spatial Memory
Learn. Mem.,
July 1, 2002;
9(4):
156 - 166.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. K. Dash, S. A. Mach, S. Blum, and A. N. Moore
Intrahippocampal Wortmannin Infusion Enhances Long-Term Spatial and Contextual Memories
Learn. Mem.,
July 1, 2002;
9(4):
167 - 177.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Rosenblum, M. Futter, K. Voss, M. Erent, P. A. Skehel, P. French, L. Obosi, M. W. Jones, and T. V. P. Bliss
The Role of Extracellular Regulated Kinases I/II in Late-Phase Long-Term Potentiation
J. Neurosci.,
July 1, 2002;
22(13):
5432 - 5441.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. R. Gerfen, S. Miyachi, R. Paletzki, and P. Brown
D1 Dopamine Receptor Supersensitivity in the Dopamine-Depleted Striatum Results from a Switch in the Regulation of ERK1/2/MAP Kinase
J. Neurosci.,
June 15, 2002;
22(12):
5042 - 5054.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. T. Dineley, X. Xia, D. Bui, J. D. Sweatt, and H. Zheng
Accelerated Plaque Accumulation, Associative Learning Deficits, and Up-regulation of alpha 7 Nicotinic Receptor Protein in Transgenic Mice Co-expressing Mutant Human Presenilin 1 and Amyloid Precursor Proteins
J. Biol. Chem.,
June 14, 2002;
277(25):
22768 - 22780.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Watanabe, D. A. Hoffman, M. Migliore, and D. Johnston
Dendritic K+ channels contribute to spike-timing dependent long-term potentiation in hippocampal pyramidal neurons
PNAS,
June 11, 2002;
99(12):
8366 - 8371.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Wu, J. Li, K.-P. Huang, and F. L. Huang
Attenuation of Protein Kinase C and cAMP-dependent Protein Kinase Signal Transduction in the Neurogranin Knockout Mouse
J. Biol. Chem.,
May 24, 2002;
277(22):
19498 - 19505.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Vanhoose, M. Emery, L. Jimenez, and D. G. Winder
ERK Activation by G-protein-coupled Receptors in Mouse Brain Is Receptor Identity-specific
J. Biol. Chem.,
March 8, 2002;
277(11):
9049 - 9053.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Stanciu and D. B. DeFranco
Prolonged Nuclear Retention of Activated Extracellular Signal-regulated Protein Kinase Promotes Cell Death Generated by Oxidative Toxicity or Proteasome Inhibition in a Neuronal Cell Line
J. Biol. Chem.,
February 1, 2002;
277(6):
4010 - 4017.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Bi, M. R. Foy, R.-M. Vouimba, R. F. Thompson, and M. Baudry
Cyclic changes in estradiol regulate synaptic plasticity through the MAP kinase pathway
PNAS,
October 25, 2001;
(2001)
241507698.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Zhen, W. Du, A. G. Romano, E. Friedman, and J. A. Harvey
The p38 Mitogen-Activated Protein Kinase Is Involved in Associative Learning in Rabbits
J. Neurosci.,
August 1, 2001;
21(15):
5513 - 5519.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. D. Cristo, N. Berardi, L. Cancedda, T. Pizzorusso, E. Putignano, G. M. Ratto, and L. Maffei
Requirement of ERK Activation for Visual Cortical Plasticity
Science,
June 22, 2001;
292(5525):
2337 - 2340.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. T. Dineley, M. Westerman, D. Bui, K. Bell, K. H. Ashe, and J. D. Sweatt
{beta}-Amyloid Activates the Mitogen-Activated Protein Kinase Cascade via Hippocampal {alpha}7 Nicotinic Acetylcholine Receptors: In Vitro and In Vivo Mechanisms Related to Alzheimer's Disease
J. Neurosci.,
June 15, 2001;
21(12):
4125 - 4133.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. L. Purcell and T. J. Carew
Modulation of Excitability in Aplysia Tail Sensory Neurons by Tyrosine Kinases
| |
