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

Eva Bollen; Daniela Puzzo; Kris Rutten; Lucia Privitera; Jochen De Vry; Tim Vanmierlo; Gunter Kenis; Agostino Palmeri; Rudi D'Hooge; Detlef Balschun; Harry M W Steinbusch; Arjan Blokland; Jos Prickaerts

doi:10.1038/npp.2014.106

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

Neuropsychopharmacology. 2014 Oct;39(11):2497-505. doi: 10.1038/npp.2014.106. Epub 2014 May 12.

Affiliations

¹ Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.
² Department of Bio-Medical Sciences, Section of Physiology, University of Catania, Catania, Italy.
³ Laboratory of Biological Psychology, Faculty of Psychology and Educational Sciences, University of Leuven, Leuven, Belgium.
⁴ Department of Neuropsychology and Psychopharmacology, Maastricht University, Maastricht, The Netherlands.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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
Long-Term Potentiation / drug effects
Long-Term Potentiation / physiology*
Male
Memory, Long-Term / drug effects
Memory, Long-Term / physiology*
Mice, Inbred C57BL
Neuropsychological Tests
Rats, Wistar
Recognition, Psychology / drug effects
Recognition, Psychology / physiology
Signal Transduction
Tissue Culture Techniques

Substances

Cyclic AMP
Cyclic AMP-Dependent Protein Kinases
Cyclic GMP-Dependent Protein Kinases
Cyclic Nucleotide Phosphodiesterases, Type 2
Cyclic Nucleotide Phosphodiesterases, Type 4
Cyclic Nucleotide Phosphodiesterases, Type 5
Cyclic GMP