The activity of many different types of molecules is modulated in the relevant neurons as an animal learns and stores information. Past research has focused on some part of these types including molecules involved in second messenger metabolism, receptors and some transcription factors. The research proposed here is directed at understanding the roles for one class of adhesion molecules, the integrins, in synaptic and behavioral plasticity. Antibodies against several different mouse integrins will be prepared to help elucidate the specific patterns of expression in the brain. The regulation of integrin genes will be examined to determine if neural activity is a factor that modulates integrin gene expression and function. Mouse knockouts for some integrin genes will be constructed and tested for alterations in synaptic plasticity, including hippocampal long-term potentiation, short-term potentiation, and long term depression. The knockout animals will also be trained in several different learning situations, including hippocampal-dependent spatial tasks, amygdala-dependent classical conditioning and conditioned taste aversion. The proposed research will reveal insights about how this important class of cell adhesion molecules serves learning and memory. In addition, the research may highlight possible points of molecular dysfunction underlying cognitive diseases.
