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The Journal of Neuroscience, February 23, 2005, 25(8):2138-2145; doi:10.1523/JNEUROSCI.3530-04.2005

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Behavioral/Systems/Cognitive
Impaired Synaptic Plasticity and Learning in Mice Lacking -Adducin, an Actin-Regulating Protein

Rebecca L. Rabenstein,¹ Nii A. Addy,¹ Barbara J. Caldarone,² Yukiko Asaka,³ Lore M. Gruenbaum,⁴ Luanne L. Peters,⁵ Diana M. Gilligan,^6,7 Reiko M. Fitzsimonds,³ and Marina R. Picciotto^1,2

¹Interdepartmental Neuroscience Program and Departments of ²Psychiatry and ³Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06508, ⁴Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877-0368, ⁵The Jackson Laboratory, Bar Harbor, Maine 04609, ⁶Puget Sound Blood Center, Seattle, Washington 98104, and ⁷University of Washington, Seattle, Washington 98195

The adducin family of proteins interacts with the actin cytoskeleton and the plasma membrane in a calcium- and cAMP-dependent manner. Thus, adducins may be involved in changes in cytoskeletal organization resulting from synaptic stimulation. -Adducin knock-out mice were examined in physiological and behavioral paradigms related to synaptic plasticity to elucidate the role the adducin family plays in processes underlying learning and memory. In situ hybridization for - and -adducin demonstrates that these mRNAs are found throughout the brain, with high levels of expression in the hippocampus. Schaffer collateral-CA1 tetanic long-term potentiation decayed rapidly in acute hippocampal slices from -adducin knock-out mice, although baseline spine morphology and postsynaptic density were normal. Interestingly, the input-output relationship was significantly increased in hippocampal slices from -adducin knock-out mice. Furthermore, -adducin knock-out mice were impaired in performance of fear conditioning and the water maze paradigm. The current results indicate that -adducin may play an important role in the cellular mechanisms underlying activity-dependent synaptic plasticity associated with learning and memory.

Key words: cytoskeleton; memory; LTP; Morris water maze; fear conditioning; dendritic spines

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Received Aug 26, 2004; revised January 12, 2005; accepted January 12, 2005.

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