title: Regulation of hippocampal synaptic plasticity thresholds and changes in exploratory and learning behavior in dominant negative NPR-B mutant rats.
abstract: The second messenger cyclic GMP affects synaptic transmission and modulates synaptic plasticity and certain types of learning and memory processes. The impact of the natriuretic peptide receptor B (NPR-B) and its ligand C-type natriuretic peptide (CNP), one of several cGMP producing signaling systems, on hippocampal synaptic plasticity and learning is, however, less well understood. We have previously shown that the NPR-B ligand CNP increases the magnitude of long-term depression (LTD) in hippocampal area CA1, while reducing the induction of long-term potentiation (LTP). We have extended this line of research to show that bidirectional plasticity is affected in the opposite way in rats expressing a dominant-negative mutant of NPR-B (NSE-NPR-BΔKC) lacking the intracellular guanylyl cyclase domain under control of a promoter for neuron-specific enolase. The brain cells of these transgenic rats express functional dimers of the NPR-B receptor containing the dominant-negative NPR-BΔKC mutant, and therefore show decreased CNP-stimulated cGMP-production in brain membranes. The NPR-B transgenic rats display enhanced LTP but reduced LTD in hippocampal slices. When the frequency-dependence of synaptic modification to afferent stimulation in the range of 1-100 Hz was assessed in transgenic rats, the threshold for both, LTP and LTD induction, was shifted to lower frequencies. In parallel, NPR-BΔKC rats exhibited an enhancement in exploratory and learning behavior. These results indicate that bidirectional plasticity and learning and memory mechanism are affected in transgenic rats expressing a dominant-negative mutant of NPR-B. Our data substantiate the hypothesis that NPR-B-dependent cGMP signaling has a modulatory role for synaptic information storage and learning.
authors.affiliation: Guest Group, In vitro-Electrophysiology Laboratory, Department of Neurophysiology, Medical Faculty, Ruhr University Bochum Bochum, Germany ; Department of Neurophysiology, Medical Faculty, Ruhr University Bochum Bochum, Germany.
authors.forename: Gleb
authors.initials: G
authors.lastname: Barmashenko
authors.affiliation: Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine, Charité Medical Faculty Berlin, Germany ; Max Delbrück Center for Molecular Medicine Berlin, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Buttgereit
authors.affiliation: Max Delbrück Center for Molecular Medicine Berlin, Germany ; Department of Physiology, Anatomy and Genetics, Burdon Sanderson Cardiac Science Centre - BHF Centre of Research Excellence, University of Oxford Oxford, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: Herring
authors.affiliation: Max Delbrück Center for Molecular Medicine Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
authors.affiliation: Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine, Charité Medical Faculty Berlin, Germany ; Max Delbrück Center for Molecular Medicine Berlin, Germany.
authors.forename: Cemil
authors.initials: C
authors.lastname: Ozcelik
authors.affiliation: Department of Neurophysiology, Medical Faculty, Ruhr University Bochum Bochum, Germany.
authors.forename: Denise
authors.initials: D
authors.lastname: Manahan-Vaughan
authors.affiliation: Guest Group, In vitro-Electrophysiology Laboratory, Department of Neurophysiology, Medical Faculty, Ruhr University Bochum Bochum, Germany.
authors.forename: Karl H
authors.initials: KH
authors.lastname: Braunewell
keywords: LTD; LTP; NPR-B; cGMP; exploratory; hippocampus; memory; metaplasticity