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.
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.
Kleppisch
Thomas
T
Institut für Pharmakologie und Toxikologie, 80802 München, Germany, Max-Planck-Institut für Psychiatrie, 80804 München, Germany. kleppisch@ipt.med.tu-muenchen.de
Wolfsgruber
Wiebke
W
Feil
Susanne
S
Allmann
Rüdiger
R
Wotjak
Carsten T
CT
Goebbels
Sandra
S
Nave
Klaus-Armin
KA
Hofmann
Franz
F
Feil
Robert
R
D000367:Age Factors; D000818:Animals; D003213:Conditioning, Psychological / Q000502:physiology; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D017869:Cyclic GMP-Dependent Protein Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000502:physiology*; D019426:Integrases / Q000378:metabolism; D007858:Learning / Q000502:physiology; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000502:physiology; D009928:Organ Specificity / Q000235:genetics; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D013028:Space Perception / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D013826:Theta Rhythm; D014764:Viral Proteins / Q000378:metabolism
D011500:Protein Synthesis Inhibitors; D014764:Viral Proteins; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D017869:Cyclic GMP-Dependent Protein Kinases; C569720:Prkg1 protein, mouse; C045073:Cre recombinase; D019426:Integrases