Differential effects of dopamine signalling on long-term memory formation and consolidation in rodent brain

Proteome Science

Research Article

Rainer Pielot¹  Eckart D Gundelfinger²  Thilo Kähne³  Michael Naumann³  Daniela C Dieterich⁴  Horst Schicknick⁵  Karl-Heinz Smalla⁶  Wolfgang Tischmeyer⁶  Ulrike Herrmann⁷  Nicole Reichenbach⁸ 

[1] Department Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, 39118, Magdeburg, Germany;Department Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, 39118, Magdeburg, Germany;Center for Behavioral Brain Sciences, 39106, Magdeburg, Germany;Molecular Neurobiology, Medical Faculty, Otto-von-Guericke-University Magdeburg, 39120, Magdeburg, Germany;Institute of Experimental Internal Medicine, Medical School, Otto von Guericke University, 39120, Magdeburg, Germany;Research Group Neuralomics, Leibniz Institute for Neurobiology, 39118, Magdeburg, Germany;Institute for Pharmacology and Toxicology, Medical Faculty, Otto-von-Guericke-University Magdeburg, 39120, Magdeburg, Germany;Center for Behavioral Brain Sciences, 39106, Magdeburg, Germany;Special Lab Molecular Biological Techniques, Leibniz Institute for Neurobiology, 39118, Magdeburg, Germany;Special Lab Molecular Biological Techniques, Leibniz Institute for Neurobiology, 39118, Magdeburg, Germany;Center for Behavioral Brain Sciences, 39106, Magdeburg, Germany;Special Lab Molecular Biological Techniques, Leibniz Institute for Neurobiology, 39118, Magdeburg, Germany;Present address: Division of Cellular Neurobiology, Zoological Institute, TU Braunschweig, 38106, Braunschweig, Germany;Special Lab Molecular Biological Techniques, Leibniz Institute for Neurobiology, 39118, Magdeburg, Germany;Present address: Research Group Neurovascular Diseases, German Center for Neurodegenerative Diseases (DZNE), Ludwig-Erhard-Allee 2, 53175, Bonn, Germany;

关键词: Dopamine agonist;    Brain;    Cortex;    Hippocampus;    Striatum;    α-synuclein;    Auditory discrimination learning;    Memory consolidation;    Proteome;    2D gel;   

DOI  :  10.1186/s12953-015-0069-2

 received in 2014-11-14, accepted in 2015-02-25,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundUsing auditory discrimination learning in gerbils, we have previously shown that activation of auditory-cortical D1/D5 dopamine receptors facilitates mTOR-mediated, protein synthesis-dependent mechanisms of memory consolidation and anterograde memory formation. To understand molecular mechanisms of this facilitatory effect, we tested the impact of local pharmacological activation of different D1/D5 dopamine receptor signalling modes in the auditory cortex. To this end, protein patterns in soluble and synaptic protein-enriched fractions from cortical, hippocampal and striatal brain regions of ligand- and vehicle-treated gerbils were analysed by 2D gel electrophoresis and mass spectrometry 24 h after intervention.ResultsAfter auditory-cortical injection of SKF38393 – a D1/D5 dopamine receptor-selective agonist reported to activate the downstream effectors adenylyl cyclase and phospholipase C – prominent proteomic alterations compared to vehicle-treated controls appeared in the auditory cortex, striatum, and hippocampus, whereas only minor changes were detectable in the frontal cortex. In contrast, auditory-cortical injection of SKF83959 – a D1/D5 agonist reported to preferentially stimulate phospholipase C – induced pronounced changes in the frontal cortex. At the molecular level, we detected altered regulation of cytoskeletal and scaffolding proteins, changes in proteins with functions in energy metabolism, local protein synthesis, and synaptic signalling. Interestingly, abundance and/or subcellular localisation of the predominantly presynaptic protein α-synuclein displayed dopaminergic regulation. To assess the role of α-synuclein for dopaminergic mechanisms of memory modulation, we tested the impact of post-conditioning systemic pharmacological activation of different D1/D5 dopamine receptor signalling modes on auditory discrimination learning in α-synuclein-mutant mice. In C57BL/6JOlaHsd mice, bearing a spontaneous deletion of the α-synuclein-encoding gene, but not in the related substrains C57BL/6JCrl and C57BL/6JRccHsd, adenylyl cyclase-mediated signalling affected acquisition rates over future learning episodes, whereas phospholipase C-mediated signalling affected final memory performance.ConclusionsDopamine signalling modes via D1/D5 receptors in the auditory cortex differentially impact protein profiles related to rearrangement of cytomatrices, energy metabolism, and synaptic neurotransmission in cortical, hippocampal, and basal brain structures. Altered dopamine neurotransmission in α-synuclein-deficient mice revealed that distinct D1/D5 receptor signalling modes may control different aspects of memory consolidation.

【 授权许可】

Unknown   
© Reichenbach et al.; licensee BioMed Central. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.