Nitric oxide (NO) has been shown to act as a retrograde messenger during the induction of long-term potentiation (LTP) of synaptic transmission ( Bohme et al., 1991 Schuman and Madison, 1991 Arancio et al., 1996 Kantor et al., 1996 Son et al., 1996 Wilson et al., 1999). The functional significance of hippocampal cGKI yet remains essentially unknown. Although the expression level of cGKII in the hippocampus is marginal, cGKI is well expressed throughout all cellular layers of the hippocampal formation ( el-Husseini et al., 1995 Kleppisch et al., 1999 de Vente et al., 2001). In vertebrates, two genes encoding cGMP-dependent protein kinases (cGKs), cGKI and cGKII, are known ( Wernet et al., 1989 Uhler, 1993). 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. Despite their deficit in LTP, adult cGKI hko mutants showed normal performance in a discriminatory water maze and had intact contextual fear conditioning. The difference in LTP between adult control and cGKI hko mice was abolished by the protein synthesis inhibitor anisomycin, suggesting that the impairment of LTP in adult cGKI hko mice reflects a defect in late-phase LTP. 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) cGKI hko mice. Unlike conventional cGKI knock-out mice, cGKI hko 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. To address these issues, we generated mice with a hippocampus-specific deletion of cGKI (cGKI hko mice).

In addition, whether cGKI is involved in spatial learning has not been investigated.

CGMP-dependent protein kinase I (cGKI) is expressed in the hippocampus, but its role in hippocampal long-term potentiation (LTP) is controversial.

Dr franz hofmann