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The Journal of Neuroscience, August 6, 2003, 23(18):7107-7116

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Integrin Requirement for Hippocampal Synaptic Plasticity and Spatial Memory

Chi-Shing Chan,1 Edwin J. Weeber,3 Sindhu Kurup,1 J. David Sweatt,3 and Ronald L. Davis1,2

Departments of 1Molecular and Cellular Biology and 2Psychiatry and Behavioral Sciences, 3Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030

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 {alpha}3 and {alpha}5, are expressed broadly in the adult mouse brain and are associated with synapses. Mice with genetically reduced expression of {alpha}3 integrin fail to maintain long-term potentiation (LTP) generated in hippocampal CA1 neurons. Mice with reduced expression of the {alpha}3 and {alpha}5 integrins exhibit a defect in paired-pulse facilitation. Mice with reduced expression of {alpha}3, {alpha}5, and {alpha}8 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.

Key words: integrins; synaptic plasticity; PPF; LTP; learning and memory; behaviors

Received Mar. 26, 2003; revised May. 16, 2003; accepted May. 28, 2003.




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