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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH079407-04
Application #
8113426
Study Section
Synapses, Cytoskeleton and Trafficking Study Section (SYN)
Program Officer
Asanuma, Chiiko
Project Start
2008-08-01
Project End
2013-07-31
Budget Start
2011-08-01
Budget End
2012-07-31
Support Year
4
Fiscal Year
2011
Total Cost
$361,969
Indirect Cost
Name
Boston University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
049435266
City
Boston
State
MA
Country
United States
Zip Code
02215
Gauthier, Jamie M; Lin, Amy; Nic Dhonnchadha, Bríd Á et al. (2017) Environmental enrichment facilitates cocaine-cue extinction, deters reacquisition of cocaine self-administration and alters AMPAR GluA1 expression and phosphorylation. Addict Biol 22:152-162
Wang, Guan; Li, Shaomin; Gilbert, James et al. (2017) Crucial Roles for SIRT2 and AMPA Receptor Acetylation in Synaptic Plasticity and Memory. Cell Rep 20:1335-1347
Gilbert, James; Man, Heng-Ye (2017) Fundamental Elements in Autism: From Neurogenesis and Neurite Growth to Synaptic Plasticity. Front Cell Neurosci 11:359
Kohman, Richie E; Cha, Susie S; Man, Heng-Ye et al. (2016) Light-Triggered Release of Bioactive Molecules from DNA Nanostructures. Nano Lett 16:2781-5
Gilbert, James; Shu, Shu; Yang, Xin et al. (2016) ?-Amyloid triggers aberrant over-scaling of homeostatic synaptic plasticity. Acta Neuropathol Commun 4:131
Gilbert, James; Man, Heng-Ye (2016) The X-Linked Autism Protein KIAA2022/KIDLIA Regulates Neurite Outgrowth via N-Cadherin and ?-Catenin Signaling. eNeuro 3:
Ning, Luwen; Li, Zhoufang; Wang, Guan et al. (2015) Quantitative assessment of single-cell whole genome amplification methods for detecting copy number variation using hippocampal neurons. Sci Rep 5:11415
Liu, D; Wei, N; Man, H-Y et al. (2015) The MT2 receptor stimulates axonogenesis and enhances synaptic transmission by activating Akt signaling. Cell Death Differ 22:583-96
Huo, Yuda; Khatri, Natasha; Hou, Qingming et al. (2015) The deubiquitinating enzyme USP46 regulates AMPA receptor ubiquitination and trafficking. J Neurochem 134:1067-80
Wang, Guan; Amato, Stephen; Gilbert, James et al. (2015) Resveratrol up-regulates AMPA receptor expression via AMP-activated protein kinase-mediated protein translation. Neuropharmacology 95:144-53

Showing the most recent 10 out of 22 publications