QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, October 3, 2007, 27(40):10765-10776; doi:10.1523/JNEUROSCI.0117-07.2007

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Satoh, Y. Articles by Takishima, K. Search for Related Content PubMed PubMed Citation Articles by Satoh, Y. Articles by Takishima, K.

 Previous Article  |  Next Article 

Behavioral/Systems/Cognitive
Extracellular Signal-Regulated Kinase 2 (ERK2) Knockdown Mice Show Deficits in Long-Term Memory; ERK2 Has a Specific Function in Learning and Memory

Yasushi Satoh,¹ Shogo Endo,⁵ Toshio Ikeda,⁶ Kazuyuki Yamada,⁷ Masataka Ito,² Masahiko Kuroki,³ Takeshi Hiramoto,⁴ Osamu Imamura,¹ Yasushi Kobayashi,³ Yasuhiro Watanabe,⁴ Shigeyoshi Itohara,⁸ and Kunio Takishima¹

Departments of ¹Biochemistry, ²Developmental Anatomy and Regenerative Biology, ³Anatomy and Neurobiology, and ⁴Pharmacology, National Defense Medical College, Tokorozawa 359-8513, Japan, ⁵ Unit for Molecular Neurobiology of Learning and Memory, Initial Research Project, Okinawa Institute of Science and Technology, Uruma 904-2234, Japan, ⁶Laboratory of Experimental Animal Model Research, National Center for Geriatrics and Gerontology, Morioka-machi, Obu 474-8511, Japan, and ⁷Research Resource Center and ⁸Laboratory for Behavioral Genetics, Brain Science Institute, RIKEN, Wako, 351-0198, Japan

Correspondence should be addressed to Dr. Kunio Takishima or Dr. Yasushi Satoh, Department of Biochemistry, National Defense Medical College, 3-2 Namiki, Tokorozawa 359-8513, Japan. Email: ktakishi{at}ndmc.ac.jp or Email: ys{at}ndmc.ac.jp

The extracellular signal-regulated kinase (ERK) 1 and 2 are important signaling components implicated in learning and memory. These isoforms display a high degree of sequence homology and share a similar substrate profile. However, recent findings suggest that these isoforms may have distinct roles: whereas ERK1 seems to be not so important for associative learning, ERK2 might be critically involved in learning and memory. Thus, the individual role of ERK2 has received considerable attention, although it is yet to be understood. Here, we have generated a series of mice in which ERK2 expression decreased in an allele dose-dependent manner. Null ERK2 knock-out mice were embryonic lethal, and the heterozygous mice were anatomically impaired. To gain a better understanding of the influence of ERK2 on learning and memory, we also generated knockdown mice in which ERK2 expression was partially (20–40%) reduced. These mutant mice were viable and fertile with normal appearance. The mutant mice showed a deficit in long-term memory in classical fear conditioning, whereas short-term memory was normal. The mice also showed learning deficit in the water maze and the eight-arm radial maze. The ERK1 expression level of the knockdown mice was comparable with the wild-type control. Together, our results indicate a noncompensable role of ERK2-dependent signal transduction in learning and memory.

Key words: knock-out mice; extracellular signal-regulated kinase 2 (ERK2); long-term memory; fear conditioning; water maze; eight-arm radial maze

---

Received Jan. 10, 2007; revised Aug. 2, 2007; accepted Aug. 3, 2007.

Correspondence should be addressed to Dr. Kunio Takishima or Dr. Yasushi Satoh, Department of Biochemistry, National Defense Medical College, 3-2 Namiki, Tokorozawa 359-8513, Japan. Email: ktakishi{at}ndmc.ac.jp or Email: ys{at}ndmc.ac.jp

This article has been cited by other articles:

				J. A. Dickinson, J. N. C. Kew, and S. Wonnacott Presynaptic {alpha}7- and {beta}2-Containing Nicotinic Acetylcholine Receptors Modulate Excitatory Amino Acid Release from Rat Prefrontal Cortex Nerve Terminals via Distinct Cellular Mechanisms Mol. Pharmacol., August 1, 2008; 74(2): 348 - 359. [Abstract] [Full Text] [PDF]

				I. S. Samuels, J. C. Karlo, A. N. Faruzzi, K. Pickering, K. Herrup, J. D. Sweatt, S. C. Saitta, and G. E. Landreth Deletion of ERK2 Mitogen-Activated Protein Kinase Identifies Its Key Roles in Cortical Neurogenesis and Cognitive Function J. Neurosci., July 2, 2008; 28(27): 6983 - 6995. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help