In the central nervous system, a neuron receives a large number of synaptic inputs from many surrounding cells, with individual synapses acting independently of one another. Synaptic plasticity, which is essential for high brain functions including learning and memory, is a synapse autonomous event under physiological conditions. A large amount of data has shown that both Hebbian-type synaptic plasticity including long-term potentiation (LTP) and long-term depression (LTD), as well as non-Hebbian type homeostatic synaptic plasticity are expressed via regulation of synaptic AMPA receptor (AMPAR) abundance, often by vesicle-mediated receptor trafficking. Given the fact that plasticity is highly synapse specific, investigation of synapse specific, activity-dependent regulation of AMPAR expression will provide crucial insights in our understanding of synapse physiology and brain function. Furthermore, homeostatic plasticity has been studied only at the neuronal population level;if and how it is expressed at single synapses remains elusive. To address these issues, we have set up two experimental paradigms in neuronal culture, in which activity levels of identifiable single synapses are specifically regulated. We will investigate the cellular mechanisms by which AMPAR abundance is specifically regulated in response to activity changes at single synapses. The application aims to understand the mechanisms by which the strength of intercellular communication is regulated in neurons. By investigating synapse specific, activity-dependent regulation of AMPAR expression, this study will provide crucial insights in our understanding of synapse physiology and brain function.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
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Synapses, Cytoskeleton and Trafficking Study Section (SYN)
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Asanuma, Chiiko
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Boston University
Schools of Arts and Sciences
United States
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Lin, Amy; Man, Heng-Ye (2014) Endocytic adaptor epidermal growth factor receptor substrate 15 (Eps15) is involved in the trafficking of ubiquitinated ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. J Biol Chem 289:24652-64
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Hou, Qingming; Gilbert, James; Man, Heng-Ye (2011) Homeostatic regulation of AMPA receptor trafficking and degradation by light-controlled single-synaptic activation. Neuron 72:806-18
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