Die Rolle von neuronalen Gap-Junctions für Lernen und Gedächtnis
Zusammenfassung der Projektergebnisse
Gap junctions in the brain mediate intercellular communication and have been implicated in several human diseases. They mediate the synchronisation, and rhythmic oscillation of neuronal activity in several brain regions. We have investigated the behavioral implications of connexion proteins specifically expressed in neurons by using 5 different gap junction-related mouse mutants including Cx36 deficient, Cx31.1 deficient, neuron-specific Cx45 deficient, Cx30.2 deficient and the neuron-specific Cx43 over-expression mice. Our results strongly suggest that neuronal gap-junctions play an important role in general activity, motor and emotional behavior as well as recognition memory. We have also investigated the molecular neurochemical and electrophysiological correlates of these behavioural phenotypes. Another research focus was the involvement of inter-cellular communication via gap junctions for the development of myelin-related human diseases. Cx30/Cx47 double deficient mice exhibit a severe myelin pathology which was correlated with impaired performance in the acquisition and retention of a rotarod task as well as behavioral alterations in the open field. These studies demonstrated that panglial gap junctional communication is essential for maintenance of myelin. Furthermore. we examined whether mCx47M282T mice which express a Cx47 missense mutation that causes Pelizaeus-Merzbacher like disease in humans show behavioral impairments in the novel object recognition, open-field and rotarod test related to their myelin pathology.
Projektbezogene Publikationen (Auswahl)
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Behavioral alterations and changes in Ca/Calmodulin kinase II levels in the striatum of connexin36 deficient mice. Behavioural Brain Research 226. 293-300
Zlomuzica A, Viggiano D, Degen J, Binder S, Ruocco LA, Sadile AG, Willecke K, Huston JP, Dere E
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(2008). Connexin31.1 deficiency in the mouse impairs object memory'and modulates open-field exploration. AChE levels in the striatum, and CREB levels in the striatum and piriform cortex. Neuroscience 153, 396-405
Dere E, Zheng-Fischhöfer Q, Viaggiano D, Gironi Camevale UA, Rocco LA, Zlomuzica A, Schnichels M, Willecke K, Huston JP, Sadile A
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(2009). Behavioral and neurochemical phenotyping of conditional neuron-directed deletion oif the gap junction Connexin45 in the mouse. The Society for Neuroscience (SFN). Annual Meeting, October 17-21, Chicago, Ill, USA
Dere E , Zlomuzica A, Schäble S, Wörsdörfer P, Degen J, May E, Willecke K, Huston JP, De Souza Silva MA
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(2009). The Connexin47M282T mouse mutant as a model for hereditary Pelizaeus-Merzbacher-like disease in humans. International Gap Junction Conference 2009, July 25-30, Sedona, AiZ. USA
Tress O, Maglione M, Zlomuzica A, Dere E, Bauer R, Degen J, Hartmann D, Kettenmann H, Willecke K
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(2010). Deletion of connexin45 in mouse neurons disrupts one-trial object recognition and alters kainate-induced gamma-oscillations in the hippocampus. Physiology and Behavior 101. 245-253
Zlomuzica A, Reichinnek S, Maxeiner S, Both M, May E, Wörsdörfer P, Draguhn A, Willecke K, Dere E
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(2010). Loss of oligodendrocyte-to-astrocyte coupling in mice double deficient for Connexin47 and Connexin30 leads to hypomyelination in cerebellar white matter. The Federation of European Neuroscience Societies (FENS), July 3.-7., Amsterdam. The Netherlands
Maglione M, Tress O, Pivneva T, Seyfarth J, May D, Dere E, Zlomuzica A, Willecke K, Kettenmann H
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(2010). Myelination in the mouse cerebellar white matter depends on oligodendrocyte to astrocyte coupling mediated by Connexin47 and Connexin30. Berlin Neuroscience Forum (BNF), June 10.-11.2010, Congress Hotel "Preußischer Hof", Liebenwalde
Maglione M, Tress O, Pivneva T, Seyfarth J, May D, Dere E, Zlomuzica A, Willecke K, Kettenmann H
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(2011). Pathologic and Phenotypic Alterations in a Mouse Expressing a Connexin47 Missense Mutation Associated with Pelizaeus-Merzbacher Like Disease in Humans. PLOS Genetics 7: e1002146
Tress O, Maglione M, Zlomuzica A, May D, Dicke N, Degen J, Dere E, Kettenmann H, Hartmann D, Willecke K
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(2012). The behavioral genetics of gap junctions. Neuroscience and Biobehavioral Reviews 36, 206-217
Dere E, Zlomuzica A
