Smaller dendritic spines, weaker synaptic transmission, but enhanced spatial learning in mice lacking Shank1.
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.
Hung
Albert Y
AY
The Institute of Physical and Chemical Research (RIKEN)-Massachusetts Institute of Technology Neuroscience Research Center, Cambridge, Massachusetts 02139, USA.
Futai
Kensuke
K
Sala
Carlo
C
Valtschanoff
Juli G
JG
Ryu
Jubin
J
Woodworth
Mollie A
MA
Kidd
Fleur L
FL
Sung
Clifford C
CC
Miyakawa
Tsuyoshi
T
Bear
Mark F
MF
Weinberg
Richard J
RJ
Sheng
Morgan
M
D000818:Animals; D002478:Cells, Cultured; D003071:Cognition / Q000502:physiology; D049229:Dendritic Spines / Q000502:physiology / Q000648:ultrastructure*; D006624:Hippocampus / Q000166:cytology; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009154:Mutation; D009419:Nerve Tissue Proteins; D009473:Neuronal Plasticity / Q000235:genetics; D009474:Neurons / Q000378:metabolism; D018408:Patch-Clamp Techniques; D009435:Synaptic Transmission / Q000502:physiology*
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C512412:SHANK1 protein, mouse