 |
||||
|
||||
|
||||
|
||||
|
||||
The Journal of Neuroscience, July 9, 2003, 23(14):6005-6012
Previous Article | Next Article
Hippocampal cGMP-Dependent Protein Kinase I Supports an Age- and Protein Synthesis-Dependent Component of Long-Term Potentiation But Is Not Essential for Spatial Reference and Contextual Memory
Thomas Kleppisch,1 Wiebke Wolfsgruber,1 Susanne Feil,1 Rüdiger Allmann,1 Carsten T. Wotjak,2 Sandra Goebbels,3 Klaus-Armin Nave,3 Franz Hofmann,1 andRobert Feil1 1Institut für Pharmakologie und Toxikologie, 80802 München, Germany, 2Max-Planck-Institut für Psychiatrie, 80804 München, Germany, and 3Max-Planck-Institut für Experimentelle Medizin, 37075 Göttingen, Germany
cGMP-dependent protein kinase I (cGKI) is expressed in the hippocampus, but its role in hippocampal long-term potentiation (LTP) is controversial. In addition, whether cGKI is involved in spatial learning has not been investigated. To address these issues, we generated mice with a hippocampus-specific deletion of cGKI (cGKIhko mice). Unlike conventional cGKI knock-out mice, cGKIhko mice lack gastrointestinal and cardiovascular phenotypes and have a normal life expectancy, which enables us to analyze hippocampal synaptic plasticity and learning in young and adult animals. Hippocampal LTP after repetitive episodes of theta burst stimulation was impaired in adult (12–14 weeks of age) but not in juvenile (3–4 weeks of age) cGKIhko mice. The difference in LTP between adult control and cGKIhko mice was abolished by the protein synthesis inhibitor anisomycin, suggesting that the impairment of LTP in adult cGKIhko mice reflects a defect in late-phase LTP. Despite their deficit in LTP, adult cGKIhko mutants showed normal performance in a discriminatory water maze and had intact contextual fear conditioning. These results suggest that hippocampal cGKI supports an age- and protein synthesis-dependent form of hippocampal LTP, whereas it is dispensable for hippocampus-dependent spatial reference and contextual memory.
Key words: cGMP-kinase; conditional knockout; Cre recombinase; long-term potentiation; hippocampus; spatial learning; fear conditioning
Received Dec. 9, 2002; revised Apr. 1, 2003; accepted Apr. 4, 2003.
This article has been cited by other articles:
Z. Zhao, Z. Wang, Y. Gu, R. Feil, F. Hofmann, and L. Ma
Regulate Axon Branching by the Cyclic GMP Pathway via Inhibition of Glycogen Synthase Kinase 3 in Dorsal Root Ganglion Sensory Neurons
J. Neurosci., February 4, 2009; 29(5): 1350 - 1360.
[Abstract] [Full Text] [PDF]
C. Paul, F. Schoberl, P. Weinmeister, V. Micale, C. T. Wotjak, F. Hofmann, and T. Kleppisch
Signaling through cGMP-Dependent Protein Kinase I in the Amygdala Is Critical for Auditory-Cued Fear Memory and Long-Term Potentiation
J. Neurosci., December 24, 2008; 28(52): 14202 - 14212.
[Abstract] [Full Text] [PDF]
A. M. Petrov, A. R. Giniatullin, G. F. Sitdikova, and A. L. Zefirov
The Role of cGMP-Dependent Signaling Pathway in Synaptic Vesicle Cycle at the Frog Motor Nerve Terminals
J. Neurosci., December 3, 2008; 28(49): 13216 - 13222.
[Abstract] [Full Text] [PDF]
G. R. Uhl, Q.-R. Liu, T. Drgon, C. Johnson, D. Walther, J. E. Rose, S. P. David, R. Niaura, and C. Lerman
Molecular Genetics of Successful Smoking Cessation: Convergent Genome-Wide Association Study Results
Arch Gen Psychiatry, June 1, 2008; 65(6): 683 - 693.
[Abstract] [Full Text] [PDF]
G. R. Uhl, T. Drgon, Q.-R. Liu, C. Johnson, D. Walther, T. Komiyama, M. Harano, Y. Sekine, T. Inada, N. Ozaki, et al.
Genome-Wide Association for Methamphetamine Dependence: Convergent Results From 2 Samples
Arch Gen Psychiatry, March 1, 2008; 65(3): 345 - 355.
[Abstract] [Full Text] [PDF]
F. Mery, A. T. Belay, A. K.-C. So, M. B. Sokolowski, and T. J. Kawecki
From the Cover: Natural polymorphism affecting learning and memory in Drosophila
PNAS, August 7, 2007; 104(32): 13051 - 13055.
[Abstract] [Full Text] [PDF]
K. R. Kaun, T. Hendel, B. Gerber, and M. B. Sokolowski
Natural variation in Drosophila larval reward learning and memory due to a cGMP-dependent protein kinase
Learn. Mem., May 3, 2007; 14(5): 342 - 349.
[Abstract] [Full Text] [PDF]
F. Hofmann, R. Feil, T. Kleppisch, and J. Schlossmann
Function of cGMP-Dependent Protein Kinases as Revealed by Gene Deletion
Physiol Rev, January 1, 2006; 86(1): 1 - 23.
[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]
F. Hofmann
The Biology of Cyclic GMP-dependent Protein Kinases
J. Biol. Chem., January 7, 2005; 280(1): 1 - 4.
[Full Text] [PDF]
V. O'Connor, A. Genin, S. Davis, K. K. Karishma, V. Doyere, C. I. De Zeeuw, G. Sanger, S. P. Hunt, G. Richter-Levin, J. Mallet, et al.
Differential Amplification of Intron-containing Transcripts Reveals Long Term Potentiation-associated Up-regulation of Specific Pde10A Phosphodiesterase Splice Variants
J. Biol. Chem., April 16, 2004; 279(16): 15841 - 15849.
[Abstract] [Full Text] [PDF]
A. J. Susswein, A. Katzoff, N. Miller, and I. Hurwitz
Nitric Oxide and Memory
Neuroscientist, April 1, 2004; 10(2): 153 - 162.
[Abstract] [PDF]
I. Tegeder, D. Del Turco, A. Schmidtko, M. Sausbier, R. Feil, F. Hofmann, T. Deller, P. Ruth, and G. Geisslinger
Reduced inflammatory hyperalgesia with preservation of acute thermal nociception in mice lacking cGMP-dependent protein kinase I
PNAS, March 2, 2004; 101(9): 3253 - 3257.
[Abstract] [Full Text] [PDF]
R. Feil, S. M. Lohmann, H. de Jonge, U. Walter, and F. Hofmann
Cyclic GMP-Dependent Protein Kinases and the Cardiovascular System: Insights From Genetically Modified Mice
Circ. Res., November 14, 2003; 93(10): 907 - 916.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|