Regulation of hippocampal long-term potentiation by p21-activated protein kinase 1 (PAK1)

The Rho family small GTPases are critically involved in the regulation of spine and synaptic properties, but the underlying mechanisms are poorly defined. We took genetic approaches to create and analyze knockout mice deficient in the expression of the protein kinase PAK1 that is directly associated...

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Bibliographic Details
Published in:Neuropharmacology 2009-01, Vol.56 (1), p.73-80
Main Authors: Asrar, Suhail, Meng, Yanghong, Zhou, Zikai, Todorovski, Zarko, Huang, Wayne Wenyin, Jia, Zhengping
Format: Article
Language:English
Subjects:
Actin cytoskeleton
Actin Depolymerizing Factors - metabolism
Actins - metabolism
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid - pharmacology
Animals
Biophysics
Cells, Cultured
Cofilin
Dendritic Spines - ultrastructure
Electric Stimulation - methods
Excitatory Amino Acid Agonists - pharmacology
Excitatory Amino Acid Antagonists - pharmacology
Excitatory Postsynaptic Potentials - genetics
Excitatory Postsynaptic Potentials - physiology
Hippocampal long-term potentiation
Hippocampus - cytology
Hippocampus - drug effects
Hippocampus - physiology
Long-Term Potentiation - drug effects
Long-Term Potentiation - genetics
Long-Term Potentiation - physiology
Mice
Mice, Knockout
N-Methylaspartate - pharmacology
Neurons - cytology
Neurons - metabolism
p21-Activated Kinases - deficiency
p21-Activated Kinases - physiology
PAK1 knockout mice
Patch-Clamp Techniques
Quinoxalines - pharmacology
Rho GTPase
Synapses - genetics
Synapses - ultrastructure
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Summary:The Rho family small GTPases are critically involved in the regulation of spine and synaptic properties, but the underlying mechanisms are poorly defined. We took genetic approaches to create and analyze knockout mice deficient in the expression of the protein kinase PAK1 that is directly associated with and activated by the Rho GTPases. We demonstrated that while these knockout mice were normal in both basal and presynaptic function, they were selectively impaired in long-term potentiation (LTP) at hippocampal CA1 synapses. Consistent with the electrophysiological deficits, the PAK1 knockout mice showed changes in the actin cytoskeleton and the actin binding protein cofilin. These results indicate that PAK1 is critical in hippocampal synaptic plasticity via regulating cofilin activity and the actin cytoskeleton.
ISSN:0028-3908
1873-7064
DOI:10.1016/j.neuropharm.2008.06.055