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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH060420-05
Application #
6665139
Study Section
Special Emphasis Panel (ZRG1-IFCN-1 (03))
Program Officer
Asanuma, Chiiko
Project Start
1999-08-01
Project End
2005-07-31
Budget Start
2003-08-01
Budget End
2005-07-31
Support Year
5
Fiscal Year
2003
Total Cost
$400,303
Indirect Cost
Name
Baylor College of Medicine
Department
Psychiatry
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
Gai, Yunchao; Liu, Ze; Cervantes-Sandoval, Isaac et al. (2016) Drosophila SLC22A Transporter Is a Memory Suppressor Gene that Influences Cholinergic Neurotransmission to the Mushroom Bodies. Neuron 90:581-95
Ning, Lin; Tian, Li; Smirnov, Sergei et al. (2013) Interactions between ICAM-5 and ?1 integrins regulate neuronal synapse formation. J Cell Sci 126:77-89
Mortillo, Steven; Elste, Alice; Ge, Yongchao et al. (2012) Compensatory redistribution of neuroligins and N-cadherin following deletion of synaptic ?1-integrin. J Comp Neurol 520:2041-52
Chan, C-S; Chen, H; Bradley, A et al. (2010) ýý8-integrins are required for hippocampal long-term potentiation but not for hippocampal-dependent learning. Genes Brain Behav 9:402-10
Chan, Chi-Shing; Levenson, Jonathan M; Mukhopadhyay, Partha S et al. (2007) Alpha3-integrins are required for hippocampal long-term potentiation and working memory. Learn Mem 14:606-15
Chan, Chi-Shing; Weeber, Edwin J; Zong, Lin et al. (2006) Beta 1-integrins are required for hippocampal AMPA receptor-dependent synaptic transmission, synaptic plasticity, and working memory. J Neurosci 26:223-32
Davis, Ronald L (2005) Olfactory memory formation in Drosophila: from molecular to systems neuroscience. Annu Rev Neurosci 28:275-302
Chan, Chi-Shing; Weeber, Edwin J; Kurup, Sindhu et al. (2003) Integrin requirement for hippocampal synaptic plasticity and spatial memory. J Neurosci 23:7107-16
Nishihara, Eijun; Yoshida-Komiya, Hiromi; Chan, Chi-Shing et al. (2003) SRC-1 null mice exhibit moderate motor dysfunction and delayed development of cerebellar Purkinje cells. J Neurosci 23:213-22