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Altered cortical synaptic morphology and impaired memory consolidation in forebrain- specific dominant-negative PAK transgenic mice.

Molecular and cellular mechanisms for memory consolidation in the cortex are poorly known. To study the relationships between synaptic structure and function in the cortex and consolidation of long-term memory, we have generated transgenic mice in which catalytic activity of PAK, a critical regulator of actin remodeling, is inhibited in the postnatal forebrain. Cortical neurons in these mice displayed fewer dendritic spines and an increased proportion of larger synapses compared to wild-type controls. These alterations in basal synaptic morphology correlated with enhanced mean synaptic strength and impaired bidirectional synaptic modifiability (enhanced LTP and reduced LTD) in the cortex. By contrast, spine morphology and synaptic plasticity were normal in the hippocampus of these mice. Importantly, these mice exhibited specific deficits in the consolidation phase of hippocampus-dependent memory. Thus, our results provide evidence for critical relationships between synaptic morphology and bidirectional modifiability of synaptic strength in the cortex and consolidation of long-term memory.

Pubmed ID: 15182717

Authors

  • Hayashi ML
  • Choi SY
  • Rao BS
  • Jung HY
  • Lee HK
  • Zhang D
  • Chattarji S
  • Kirkwood A
  • Tonegawa S

Journal

Neuron

Publication Data

June 10, 2004

Associated Grants

None

Mesh Terms

  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Behavior, Animal
  • Blotting, Northern
  • Blotting, Western
  • Dendrites
  • Drug Interactions
  • Enzyme Activation
  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Glycine
  • Hippocampus
  • Immunohistochemistry
  • In Situ Hybridization
  • Long-Term Potentiation
  • Long-Term Synaptic Depression
  • Male
  • Maze Learning
  • Memory Disorders
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Electron
  • Models, Neurological
  • Nerve Tissue Proteins
  • Neurofilament Proteins
  • Neurons
  • Prosencephalon
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-myc
  • Rats
  • Retention (Psychology)
  • Silver Staining
  • Spatial Behavior
  • Synapses
  • Synaptophysin
  • Time Factors
  • Valine
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
  • p21-Activated Kinases