Abstract
The role of nitric oxide (NO)/cGMP signaling in long-term potentiation (LTP) has been a lingering matter of debate. Within the cascade, the NO receptor guanylyl cyclase (GC), the cGMP-forming enzyme that is stimulated by NO, plays a key role. Two isoforms of GC (alpha2-GC, alpha1-GC) exist. To evaluate their contribution to synaptic plasticity, we analyzed knock-out mice lacking either one of the GC isoforms. We found that LTP induced in the visual cortex is NO dependent in the wild-type mice, absent in either of the GC isoform-deficient mice, and restored with application of a cGMP analog in both strains. The requirement of both NO receptor GCs for LTP indicates the existence of two distinct NO/cGMP-mediated pathways, which have to work in concert for expression of LTP.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Female
-
Guanylate Cyclase / deficiency
-
Guanylate Cyclase / genetics
-
Guanylate Cyclase / physiology*
-
Isoenzymes / deficiency
-
Isoenzymes / genetics
-
Isoenzymes / physiology
-
Long-Term Potentiation / genetics
-
Long-Term Potentiation / physiology*
-
Male
-
Mice
-
Mice, Inbred C57BL
-
Mice, Knockout
-
Nitric Oxide / metabolism*
-
Nitric Oxide / physiology
-
Receptors, Cytoplasmic and Nuclear / deficiency
-
Receptors, Cytoplasmic and Nuclear / genetics
-
Receptors, Cytoplasmic and Nuclear / physiology*
-
Signal Transduction / genetics
-
Signal Transduction / physiology
-
Soluble Guanylyl Cyclase
-
Visual Cortex / enzymology*
Substances
-
Isoenzymes
-
Receptors, Cytoplasmic and Nuclear
-
Nitric Oxide
-
Guanylate Cyclase
-
Soluble Guanylyl Cyclase