Smaller dendritic spines, weaker synaptic transmission, but enhanced spatial learning in mice lacking Shank1

Albert Y. Hung, Kensuke Futai, Carlo Sala, Juli G. Valtschanoff, Jubin Ryu, Mollie A. Woodworth, Fleur L. Kidd, Clifford C. Sung, Tsuyoshi Miyakawa, Mark F. Bear, Richard J. Weinberg, Morgan Sheng

Research output: Contribution to journalArticle

214 Citations (Scopus)

Abstract

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 function in vivo, and they highlight a differential role for Shank1 in specific cognitive processes, a feature that may be relevant to human autism spectrum disorders.

Original languageEnglish
Pages (from-to)1697-1708
Number of pages12
JournalJournal of Neuroscience
Volume28
Issue number7
DOIs
Publication statusPublished - 13-02-2008

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Dendritic Spines
Synaptic Transmission
Synapses
Post-Synaptic Density
Neuronal Plasticity
Long-Term Memory
Autistic Disorder
Knockout Mice
Fear
Proteins
Anxiety
Learning
Phenotype
Neurons
Genes
Spatial Learning

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Hung, A. Y., Futai, K., Sala, C., Valtschanoff, J. G., Ryu, J., Woodworth, M. A., ... Sheng, M. (2008). Smaller dendritic spines, weaker synaptic transmission, but enhanced spatial learning in mice lacking Shank1. Journal of Neuroscience, 28(7), 1697-1708. https://doi.org/10.1523/JNEUROSCI.3032-07.2008
Hung, Albert Y. ; Futai, Kensuke ; Sala, Carlo ; Valtschanoff, Juli G. ; Ryu, Jubin ; Woodworth, Mollie A. ; Kidd, Fleur L. ; Sung, Clifford C. ; Miyakawa, Tsuyoshi ; Bear, Mark F. ; Weinberg, Richard J. ; Sheng, Morgan. / Smaller dendritic spines, weaker synaptic transmission, but enhanced spatial learning in mice lacking Shank1. In: Journal of Neuroscience. 2008 ; Vol. 28, No. 7. pp. 1697-1708.
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Hung, AY, Futai, K, Sala, C, Valtschanoff, JG, Ryu, J, Woodworth, MA, Kidd, FL, Sung, CC, Miyakawa, T, Bear, MF, Weinberg, RJ & Sheng, M 2008, 'Smaller dendritic spines, weaker synaptic transmission, but enhanced spatial learning in mice lacking Shank1', Journal of Neuroscience, vol. 28, no. 7, pp. 1697-1708. https://doi.org/10.1523/JNEUROSCI.3032-07.2008

Smaller dendritic spines, weaker synaptic transmission, but enhanced spatial learning in mice lacking Shank1. / Hung, Albert Y.; Futai, Kensuke; Sala, Carlo; Valtschanoff, Juli G.; Ryu, Jubin; Woodworth, Mollie A.; Kidd, Fleur L.; Sung, Clifford C.; Miyakawa, Tsuyoshi; Bear, Mark F.; Weinberg, Richard J.; Sheng, Morgan.

In: Journal of Neuroscience, Vol. 28, No. 7, 13.02.2008, p. 1697-1708.

Research output: Contribution to journalArticle

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AU - Futai, Kensuke

AU - Sala, Carlo

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AU - Woodworth, Mollie A.

AU - Kidd, Fleur L.

AU - Sung, Clifford C.

AU - Miyakawa, Tsuyoshi

AU - Bear, Mark F.

AU - Weinberg, Richard J.

AU - Sheng, Morgan

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