Improved long-term memory via enhancing cGMP-PKG signaling requires cAMP-PKA signaling

• Published in: Neuropsychopharmacology (New York, N.Y.) N.Y.), 2014-10, Vol.39 (11), p.2497-2505
• Main Authors: Bollen, Eva, Puzzo, Daniela, Rutten, Kris, Privitera, Lucia, De Vry, Jochen, Vanmierlo, Tim, Kenis, Gunter, Palmeri, Agostino, D'Hooge, Rudi, Balschun, Detlef, Steinbusch, Harry M W, Blokland, Arjan, Prickaerts, Jos
• Format: Article
• Language: English
• Subjects: Animals; CA1 Region, Hippocampal - drug effects; CA1 Region, Hippocampal - physiology; Cyclic AMP - metabolism; Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors; Cyclic AMP-Dependent Protein Kinases - metabolism; Cyclic GMP - metabolism; Cyclic GMP-Dependent Protein Kinases - antagonists & inhibitors; Cyclic GMP-Dependent Protein Kinases - metabolism; Cyclic Nucleotide Phosphodiesterases, Type 2 - metabolism; Cyclic Nucleotide Phosphodiesterases, Type 4 - metabolism; Cyclic Nucleotide Phosphodiesterases, Type 5 - metabolism; Kinases; Long-Term Potentiation - drug effects; Long-Term Potentiation - physiology; Male; Memory; Memory, Long-Term - drug effects; Memory, Long-Term - physiology; Mental health; Mice, Inbred C57BL; Neuropsychological Tests; Neuropsychology; Neurosciences; Original; Protein synthesis; Proteins; Rats, Wistar; Recognition (Psychology) - drug effects; Recognition (Psychology) - physiology; Signal Transduction; Tissue Culture Techniques
• ISSN: 0893-133X; 1740-634X
• DOI: 10.1038/npp.2014.106

Memory consolidation is defined by the stabilization of a memory trace after acquisition, and consists of numerous molecular cascades that mediate synaptic plasticity. Commonly, a distinction is made between an early and a late consolidation phase, in which early refers to the first hours in which labile synaptic changes occur, whereas late consolidation relates to stable and long-lasting synaptic changes induced by de novo protein synthesis. How these phases are linked at a molecular level is not yet clear. Here we studied the interaction of the cyclic nucleotide-mediated pathways during the different phases of memory consolidation in rodents. In addition, the same pathways were studied in a model of neuronal plasticity, long-term potentiation (LTP). We demonstrated that cGMP/protein kinase G (PKG) signaling mediates early memory consolidation as well as early-phase LTP, whereas cAMP/protein kinase A (PKA) signaling mediates late consolidation and late-phase-like LTP. In addition, we show for the first time that early-phase cGMP/PKG signaling requires late-phase cAMP/PKA-signaling in both LTP and long-term memory formation.