Smaller Dendritic Spines, Weaker Synaptic Transmission, but Enhanced Spatial Learning in Mice Lacking Shank1
| Autor: | Fleur L. Kidd, Kensuke Futai, Mark F. Bear, Jubin Ryu, Clifford C. Sung, Juli G. Valtschanoff, Tsuyoshi Miyakawa, Albert Y. Hung, Morgan Sheng, Carlo Sala, Mollie A. Woodworth, Richard J. Weinberg |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Patch-Clamp Techniques Dendritic spine Dendritic Spines Hippocampus Nerve Tissue Proteins Neurotransmission Biology Synaptic Transmission Article Mice Cognition Postsynaptic potential Animals Maze Learning Cells Cultured Mice Knockout Neurons Microscopy Confocal Neuronal Plasticity General Neuroscience Membrane Proteins SHANK2 Mice Inbred C57BL Mutation Synaptic plasticity Excitatory postsynaptic potential Postsynaptic density Neuroscience |
| Zdroj: | The Journal of Neuroscience. 28:1697-1708 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.3032-07.2008 |
| Popis: | Experience-dependent changes in the structure of dendritic spines may contribute to learning and memory. Encoded by three genes, the Shank family of postsynaptic scaffold proteins are abundant and enriched in the postsynaptic density (PSD) of central excitatory synapses. When expressed in cultured hippocampal neurons, Shank promotes the maturation and enlargement of dendritic spines. Recently, Shank3 has been genetically implicated in human autism, suggesting an important role for Shank proteins in normal cognitive development. Here, we report the phenotype of Shank1 knock-out mice. Shank1 mutants showed altered PSD protein composition; reduced size of dendritic spines; smaller, thinner PSDs; and weaker basal synaptic transmission. Standard measures of synaptic plasticity were normal. Behaviorally, they had increased anxiety-related behavior and impaired contextual fear memory. Remarkably, Shank1-deficient mice displayed enhanced performance in a spatial learning task; however, their long-term memory retention in this task was impaired. These results affirm the importance of Shank1 for synapse structure and functionin vivo, and they highlight a differential role for Shank1 in specific cognitive processes, a feature that may be relevant to human autism spectrum disorders. |
| Databáze: | OpenAIRE |
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