title: Integrin requirement for hippocampal synaptic plasticity and spatial memory.
abstract: The establishment of memory requires coordinated signaling between presynaptic and postsynaptic terminals in the CNS. The integrins make up a large family of cell adhesion receptors that are known to mediate bidirectional signaling between cells or between cells and their external environment. We show here that many different integrins, including alpha3 and alpha5, are expressed broadly in the adult mouse brain and are associated with synapses. Mice with genetically reduced expression of alpha3 integrin fail to maintain long-term potentiation (LTP) generated in hippocampal CA1 neurons. Mice with reduced expression of the alpha3 and alpha5 integrins exhibit a defect in paired-pulse facilitation. Mice with reduced expression of alpha3, alpha5, and alpha8 are defective in hippocampal LTP and spatial memory in the water maze but have normal fear conditioning. These results demonstrate that several different integrins are involved in physiological plasticity and provide the first evidence of their requirement for behavioral plasticity in vertebrates.
authors.affiliation: Department of Molecular and Cellular Biology, Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Chi-Shing
authors.initials: CS
authors.lastname: Chan
authors.forename: Edwin J
authors.initials: EJ
authors.lastname: Weeber
authors.forename: Sindhu
authors.initials: S
authors.lastname: Kurup
authors.forename: J David
authors.initials: JD
authors.lastname: Sweatt
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Davis
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000378:metabolism; D003214:Conditioning, Classical; D005239:Fear / Q000502:physiology; D006579:Heterozygote; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D066298:In Vitro Techniques; D016023:Integrins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017774:Long-Term Potentiation / Q000235:genetics / Q000502:physiology; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000502:physiology*; D021122:Protein Subunits / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013028:Space Perception / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D016023:Integrins; D021122:Protein Subunits; D012333:RNA, Messenger