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α8‐Integrins are required for hippocampal long‐term potentiation but not for hippocampal‐dependent learning
Authors:C‐S Chan  H Chen  A Bradley  I Dragatsis  C Rosenmund  R L Davis
Institution:1. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA;2. Present address: GlaxoSmithKline R&D China, Pudong, Shanghai, China;3. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA;4. Present address: Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK;5. Department of Physiology, The University of Tennessee Health Science Center, Memphis, TN;6. Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX;7. Present address: Department of Neuroscience, Scripps Research Institute Florida, Jupiter, FL, USA
Abstract:Integrins are heterodimeric transmembrane cell adhesion receptors that are essential for a wide range of biological functions via cell–matrix and cell–cell interactions. Recent studies have provided evidence that some of the subunits in the integrin family are involved in synaptic and behavioral plasticity. To further understand the role of integrins in the mammalian central nervous system, we generated a postnatal forebrain and excitatory neuron‐specific knockout of α8‐integrin in the mouse. Behavioral studies showed that the mutant mice are normal in multiple hippocampal‐dependent learning tasks, including a T‐maze, non‐match‐to‐place working memory task for which other integrin subunits like α3‐ and β1‐integrin are required. In contrast, mice mutant for α8‐integrin exhibited a specific impairment of long‐term potentiation (LTP) at Schaffer collateral–CA1 synapses, whereas basal synaptic transmission, paired‐pulse facilitation and long‐term depression (LTD) remained unaffected. Because LTP is also impaired in the absence of α3‐integrin, our results indicate that multiple integrin molecules are required for the normal expression of LTP, and different integrins display distinct roles in behavioral and neurophysiological processes like synaptic plasticity.
Keywords:Integrins  learning  long‐term potentiation  memory
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