The Journal of Neuroscience, February 4, 2009, 29(5):1586-1595; doi:10.1523/JNEUROSCI.4306-08.2009
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Cellular/Molecular
Enhanced NMDA Receptor-Mediated Synaptic Transmission, Enhanced Long-Term Potentiation, and Impaired Learning and Memory in Mice Lacking IRSp53
Myoung-Hwan Kim,1 *
Jeonghoon Choi,1 *
Jinhee Yang,1 *
Woosuk Chung,1 *
Ji-Hyun Kim,2
Sang Kyoo Paik,3
Karam Kim,1
Seungnam Han,1
Hyejung Won,1
Young-Soo Bae,1
Suk-Hee Cho,2
Jinsoo Seo,2
Yong Chul Bae,3
Se-Young Choi,2 and
Eunjoon Kim1
1National Creative Research Initiative Center for Synaptogenesis and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea, 2Department of Physiology, College of Dentistry and Dental Research Institute, BK21 Program, Seoul National University, Seoul 110-749, Korea, and 3Department of Anatomy and Neurobiology, BK21, School of Dentistry, Kyungpook National University, Daegu 700-412, Korea
Correspondence should be addressed to Eunjoon Kim, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea. Email: kime{at}kaist.ac.kr
IRSp53 is an adaptor protein that acts downstream of Rac and Cdc42 small GTPases and is implicated in the regulation of membrane deformation and actin filament assembly. In neurons, IRSp53 is an abundant postsynaptic protein and regulates actin-rich dendritic spines; however, its in vivo functions have not been explored. We characterized transgenic mice deficient of IRSp53 expression. Unexpectedly, IRSp53–/– neurons do not show significant changes in the density and ultrastructural morphologies of dendritic spines. Instead, IRSp53–/– neurons exhibit reduced AMPA/NMDA ratio of excitatory synaptic transmission and a selective increase in NMDA but not AMPA receptor-mediated transmission. IRSp53–/– hippocampal slices show a markedly enhanced long-term potentiation (LTP) with no changes in long-term depression. LTP-inducing theta burst stimulation enhances NMDA receptor-mediated transmission. Spatial learning and novel object recognition are impaired in IRSp53–/– mice. These results suggest that IRSp53 is involved in the regulation of NMDA receptor-mediated excitatory synaptic transmission, LTP, and learning and memory behaviors.
Key words: IRSp53; PSD-95; synapse; actin; LTP; learning and memory
Received Sept. 9, 2008;
revised Jan. 5, 2009;
accepted Jan. 6, 2009.
Correspondence should be addressed to Eunjoon Kim, Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea. Email: kime{at}kaist.ac.kr
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