The long-term goal of this laboratory is to understand the molecular mechanisms underlying synapse development and function. A number of model systems are used in our studies, including Xenopus nerve-muscle cultures, dissociated cultures of mammalian neurons, hippocampal slices and knockout mice. Our recent efforts focus on two closely related areas, using a combination of molecular biological and electrophysiological techniques: 1) to study the role of neurotrophic factors in synapse development and plasticity; 2) to isolate new genes and characterize new molecules that are involved in specific stages of synaptogenesis. We have discovered that the neurotrophin BDNF promotes the development of long-term potentiation, a cellular model for learning and memory. This effect is mediated by a potentiation of synaptic responses to high frequency stimulation. These results suggest that neurotrophins regulate synaptic maturation. We also demonstrated that endogenous synapsin I, a synaptic vesicle protein that is a target of neurotrophic regulation, is an important molecule mediating synapse maturation. Finally, we cloned the mammalian homolog of frequenin, a calcium binding protein involved in synaptic responses to high frequency stimulation.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Intramural Research (Z01)
Project #
1Z01HD000714-01
Application #
2449771
Study Section
Special Emphasis Panel (LDN)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
1996
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code
Pearce, Lisa D; Brauner-Otto, Sarah R; Ji, Yingchun (2015) Explaining religious differentials in family-size preference: Evidence from Nepal in 1996. Popul Stud (Camb) 69:23-37
Ji, Yuanyuan; Lu, Yuan; Yang, Feng et al. (2010) Acute and gradual increases in BDNF concentration elicit distinct signaling and functions in neurons. Nat Neurosci 13:302-9
Lu, Bai; Wang, Kuan Hong; Nose, Akinao (2009) Molecular mechanisms underlying neural circuit formation. Curr Opin Neurobiol 19:162-7
Lu, Yuan; Christian, Kimberly; Lu, Bai (2008) BDNF: a key regulator for protein synthesis-dependent LTP and long-term memory? Neurobiol Learn Mem 89:312-23
Nagappan, Guhan; Woo, Newton H; Lu, Bai (2008) Ama ""zinc"" link between TrkB transactivation and synaptic plasticity. Neuron 57:477-9
Galloway, Evan M; Woo, Newton H; Lu, Bai (2008) Persistent neural activity in the prefrontal cortex: a mechanism by which BDNF regulates working memory? Prog Brain Res 169:251-66
An, Juan Ji; Gharami, Kusumika; Liao, Guey-Ying et al. (2008) Distinct role of long 3'UTR BDNF mRNA in spine morphology and synaptic plasticity in hippocampal neurons. Cell 134:175-87
Martinowich, Keri; Lu, Bai (2008) Interaction between BDNF and serotonin: role in mood disorders. Neuropsychopharmacology 33:73-83
Lu, Bai; Martinowich, Keri (2008) Cell biology of BDNF and its relevance to schizophrenia. Novartis Found Symp 289:119-29;discussion 129-35, 193-5
Lu, Zhonghua; Je, Hyun-Soo; Young, Paul et al. (2007) Regulation of synaptic growth and maturation by a synapse-associated E3 ubiquitin ligase at the neuromuscular junction. J Cell Biol 177:1077-89

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