Lingjun Li

 

 

Peptidomics, Neuromodulation and Endocrine Regulation of Neural Networks

E-mail: lli@pharmacy.wisc.edu

Research Strengths: Molecular Neuroscience, Neural Circuits

One of the most striking features of biological brains is that neurons contain and release a very large number of neurotransmitters and neuromodulators. Our research aims at developing a novel mass spectrometry-based proteomics approach to answer questions about the most complex and elusive set of neuromodulators, the neuropeptides, and gain new insights into the roles of peptide modulators play in the behavior of the neuronal circuitry.

The crustacean stomatogastric nervous system (STNS) is an excellent model system for studying the neural basis of rhythmic behavior and it is also an ideal system to investigate neuromodulation in a well-defined neural network. This is an attractive preparation because of the limited number of neurons whose electrophysiological properties can be readily assessed and yet an amazingly large number of peptide neuromodulators are involved in this small neural network. However, we are far from having a complete description of all the neurotransmitters and neuropeptides contained in the STNS, which is crucial for understanding the mechanisms by which this hard-wired, pattern-generating circuitry is functionally modulated. We are developing an array of enabling mass spectrometric tools coupled with front-end microseparation strategies and back-end bioinformatics tools to provide a unique and global view of the diverse assortment of peptides contained within a small neuronal network. Once the chemical identities of the peptides are established, peptide colocalization pattern and release at the cellular and network level will be studied. Thus, our research will help to define completely how the full range of behaviors produced by a neural circuit is specified or encoded by the modulatory environment. While the functional consequences of the large diversity of neuropeptides in the nervous systems is still not fully understood, as we continue to discover and study the functional roles of additional neuropeptides and their presence in identified projection neurons, we will uncover the rules by which biological circuits can be so flexible and yet so stable in its actions.

Lab Website:

http://www.pharmacy.wisc.edu/facstaff/sciences/LiGroup/index.cfm?lk=1

Selected Publications:

• Q. Fu, L. Tang, E. Marder, and L. Li. 2007. Mass spectrometric characterization and physiological actions of VPNDWAHFRGSWamide, a novel B-type allatostatin in Cancer crabs. Journal of Neurochemistry 101: 1099-1107. [PDF]
• S.S. DeKeyser, K. K. Kutz-Naber, J. J. Schmidt, G.A. Barrett-Wilt, and L. Li. 2007. Mass spectral imaging of neuropeptides in crustacean nervous tissue by MALDI TOF/TOF. Journal of Proteome Research 6: 1782-1791. Cited by Faculty of 1000 Biology Evaluation.
• S. DeKeyser and L. Li*. 2007. Mass spectrometric charting of neuropeptides in arthropod neurons. Analytical and Bioanalytical Chemistry Invited trend article 387: 29-35.
• S.R. Saideman, M. Ma, K. K. Kutz-Naber, A. Cook, P. Torfs, L. Schoofs, L. Li, and M. P. Nusbaum. 2007. Modulation of rhythmic motor activity by pyrokinin peptides. Journal of Neurophysiology 97: 579-595.
• M. Ma, K, K. Kutz-Naber, and L. Li. 2007. Methyl esterification assisted MALDI FTMS characterization of orcokinin neuropeptide family. Analytical Chemistry 79: 673-681. [PDF]
• A. E. Christie, K. K. Kutz-Naber, E. A. Stemmler, A. Klein, D. I. Messinger, C. C. Goiney, Y.-W. A. Hsu, C. R. Easton, L. Li, and P.S. Dickinson. 2007. Midgut epithelial endocrine cells are a rich source of the neuropeptides APSGFLGMRamide (Cancer borealis tachykinin-related peptide Ia) and GYRKPPFNGSIFamide (Gly1-SIFamide) in the crabs Cancer borealis, Cancer magister and Cancer productus. J. Exp. Biol. 210: 699-714. [PDF]
• J. A. Dowell, W. Vander Heyden, and L. Li. 2006. Rat neuropeptidomics by LC/MS/MS and MALDI-FTMS: enhanced dissection and extraction techniques coupled with 2D RP-RP HPLC separation. Journal of Proteome Research. 5: 3368-3375. Featured in the Research Profile Section of Journal of Proteome Research and Bio Sphere News Section in Analytical Chemistry.
• N. Cruz-Bermudez, Q. Fu, K. Kutz, A. Christie, L. Li, and E. Marder. 2006. Mass spectrometric characterization and physiological actions of GAHKNYLRFamide, a novel FMRFamide-like peptide from crabs of the genus Cancer. J. Neurochem. 97: 784-799.
• D.J. Schulz, R.A. Baines, C.M. Hempel, L. Li, B. Liss, H. Misonou. 2006. The role of gene expression and cellular excitability in the regulation of functional neuronal identity. Journal of Neuroscience 26: 10362-10367. Invited Mini-Symposium Review.
• Li, L., R. Pulver, P. Kelley, V. Thirumalai, J.V. Sweedler, and E. Marder. 2002. Oreokinin peptides in developing and adult crustacean stomatogastric nervous systems and pericardial organs. J. Comp. Neurol. 444: 227-244. [PDF]
• Li, L., P.D. Floyd, S.S. Rubakhin, E.V. Romanova, J. Jing, V.Y. Alexeeva, N.C. Dembrow, K.R. Weiss, F.S. Vilim, and J.V. Sweedler. 2001. Cerebrin prohormone processing, distribution and action in Aplysia californica. J. Neurochem. 77: 1569-1580. [PDF]
• Li, L., R.W. Garden, and J.V. Sweedler. 2000. Single-cell MALDI: A new tool for direct peptide profiling. Trends Biotechnol. 18: 151-160. [PDF]