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The Journal of Neuroscience, October 3, 2007, 27(40):10832-10839; doi:10.1523/JNEUROSCI.2588-07.2007

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Behavioral/Systems/Cognitive
Estradiol Improves Cerebellar Memory Formation by Activating Estrogen Receptor ß

Corina E. Andreescu,¹ Bogdan A. Milojkovic,¹ Elize D. Haasdijk,¹ Piet Kramer,² Frank H. De Jong,² Andrée Krust,³ Chris I. De Zeeuw,^1,4 and Marcel T. G. De Jeu¹

Departments of ¹Neuroscience and ²Internal Medicine, Erasmus Medical Center, 3000 DR Rotterdam, The Netherlands, ³Institut de Genetique et de Biologie Moleculaire et Cellulaire, Centre National de la Recherche Scientifique/Inserm/University Louis Pasteur, College de France, 67070 Strasbourg, France, and ⁴Netherlands Institute for Neuroscience, Royal Netherlands Academy of Sciences, 1000 GC Amsterdam, The Netherlands

Correspondence should be addressed to Dr. Chris I. De Zeeuw, Department of Neuroscience, Erasmus Medical Center, Dr. Molewaterplein 50, 3000 DR Rotterdam, The Netherlands. Email: c.dezeeuw{at}erasmusmc.nl

Learning motor skills is critical for motor abilities such as driving a car or playing piano. The speed at which we learn those skills is subject to many factors. Yet, it is not known to what extent gonadal hormones can affect the achievement of accurate movements in time and space. Here we demonstrate via different lines of evidence that estradiol promotes plasticity in the cerebellar cortex underlying motor learning. First, we show that estradiol enhances induction of long-term potentiation at the parallel fiber to Purkinje cell synapse, whereas it does not affect long-term depression; second, we show that estradiol activation of estrogen receptor ß receptors in Purkinje cells significantly improves gain-decrease adaptation of the vestibulo-ocular reflex, whereas it does not affect general eye movement performance; and third, we show that estradiol increases the density of parallel fiber to Purkinje cell synapses, whereas it does not affect the density of climbing fiber synapses. We conclude that estradiol can improve motor skills by potentiating cerebellar plasticity and synapse formation. These processes may be advantageous during periods of high estradiol levels of the estrous cycle or pregnancy.

Key words: cerebellum; estrogen; motor learning; neuronal plasticity; estrogen receptor ß; mutant mice

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Received June 7, 2007; revised July 20, 2007; accepted Aug. 2, 2007.

Correspondence should be addressed to Dr. Chris I. De Zeeuw, Department of Neuroscience, Erasmus Medical Center, Dr. Molewaterplein 50, 3000 DR Rotterdam, The Netherlands. Email: c.dezeeuw{at}erasmusmc.nl

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