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

Mansuo L. Hayashi, Se Young Choi, B. S. Shankaranarayana Rao, Hae Yoon Jung, Hey Kyoung Lee, Dawei Zhang, Sumantra Chattarji, Alfredo Kirkwood, Susumu Tonegawa

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)773-787
Number of pages15
JournalNeuron
Volume42
Issue number5
DOIs
StatePublished - Jun 10 2004

ASJC Scopus subject areas

  • Neuroscience(all)

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    Hayashi, M. L., Choi, S. Y., Shankaranarayana Rao, B. S., Jung, H. Y., Lee, H. K., Zhang, D., Chattarji, S., Kirkwood, A., & Tonegawa, S. (2004). Altered cortical synaptic morphology and impaired memory consolidation in forebrain- specific dominant-negative PAK transgenic mice. Neuron, 42(5), 773-787. https://doi.org/10.1016/j.neuron.2004.05.003