Boston University Department of Biology

Faculty Profiles

Current Research

The modification in synaptic strength, or synaptic plasticity, is believed to be the molecular mechanism underpinning higher brain functions such as learning and memory. Therefore, it is of crucial importance to understand how synaptic transmission is regulated. Because information is transferred across the synapse via the binding neurotransmitters to their receptors, the localization and amount of receptors at the postsynaptic site is a major determinant of synaptic efficacy. Glutamatergic AMPA receptors (AMPARs) mediate the vast majority of excitatory synaptic transmission in the brain. It has been demonstrated that AMPARs are not static on the synaptic membrane; rather, they recycle continuously between the plasma membrane and the intracellular compartments. AMPARs are inserted to the plasma membrane via SNARE-mediated vesicle fusion and are internalized through clathrin-coated pit pathways. Alterations in AMPAR trafficking processes will lead to changes in synaptic receptor numbers and thus the strength of synaptic transmission. The main focus of our lab is to understand the cellular/molecular mechanisms underlying AMPAR synaptic localization and synaptic plasticity. The questions we address include: What molecules and signaling pathways determine AMPAR synaptic localization? How does neuronal activity regulate AMPA receptor trafficking and expression? How does the neuron maintain a specific amount of total receptors? How are receptors degraded and what regulates the rate of turnover? Using cultured cortical and hippocampal neurons and brain slices, we study receptor trafficking and synaptic transmission by employing a wide range of techniques including immunocytochemistry, confocal/fluorescence microscopy, live-imaging, biochemistry (western blotting, immunoprecipitation), and electrophysiology (patch clamp recording).

Courses Taught

• BI 455/655 Developmental Neurobiology
• BI 599 Neurobiology of Synapses

Selected Publications

• Zhang D, Hou Q, Wang M, Lin A, Navis A, Raissi A, Liu F, Man HY. (2009). Na, K-ATPase activity regulates AMPA receptor turnover through proteasome-mediated proteolysis. J Neurosci., 29 (14): 4498-4511
• Hou Q, Huang Y, Amato S, Solomon H, Snyder R, Huganir RL, Man HY. (2008).
  Regulation of AMPA receptor localization in lipid rafts. Mol. Cel. Neurosci., 38 (2): 213-223.
• Hou Q, Zhang D, Jarzylo L, Huganir RL, Man HY. (2008). Homeostatic regulation of AMPA receptor expression at single hippocampal synapses. PNAS, 105(2), 775-780.
• Man HY, Sekine-Aizawa Y, Huganir RL. (2007). Regulation of {alpha}-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor trafficking through PKA phosphorylation of the Glu receptor 1 subunit. PNAS, 104(9), 3579-84.
• Huang Y, Man HY, Sekine-Aizawa Y, Han Y, Juluri K, Luo H, Cheah J, Lowenstein C, Huganir RL, Snyder SH. (2005). S-nitrosylation of N-ethylmaleimide sensitive factor mediates surface expression of AMPA receptors. Neuron, 46(4), 533-40.
• Man HY, Wang QH, Lu WY, Ju W, Amardian G, D’Souza S, Liu LD, Wong TP, Becker LE, Pai L, Liu F, Wymann MP, MacDonald JF, Wang YT. (2003). Selective activation of AMPA receptor-associated PI3-Kinase is required for LTP induction. Neuron, 37, 611-624.
• Man HY, Lu WY, Ju W, Trimble W, Wang YT, MacDonald JF. (2001). Activation of synaptic NMDA receptors induces membrane insertion of new AMPA receptors and LTP in cultured hippocampal neurons. (* Equal contribution) Neuron, 29, 243-254.
• Man HY, Lin J, Ju W, Ahmadian G, Liu L, Becker LE, Sheng M, Wang YT. (2000). Regulation of AMPA receptor-mediated synaptic transmission by clathrin-dependent receptor internalization. Neuron, 25, 649-662.