Synapses are the essential point of contact between neurons and their targets for the directional flow of information in the nervous system. The study of how synapses form and how they function is fundamental to our understanding of nervous system connectivity and communication. It is now believed that deficiencies in synaptic function are central to many psychiatric and neurodegenerative diseases such as schizophrenia, Alzheimer’s, Parkinson’s and Huntington’s disease. Thus, it is anticipated that a better understanding of the molecular mechanisms that control these highly specialized structures holds great promise for the development of urgently needed, novel therapies for these diseases.
The principle research objective of my laboratory is to elucidate the cellular and molecular mechanisms underlying the formation, stability, and elimination of CNS synapses. We primarily utilize cultured hippocampal neurons as a model system, and extend these studies to genetically modified mouse models when appropriate. Fundamental questions addressed in the lab include; 1) how does cell-cell contact result in the assembly of pre- and postsynaptic compartments, 2) what are the contributions of pre- and postsynaptic elements to the integrity of the synapse, 3) what are the transsynaptic signals that regulate synaptic plasticity, and 4) is synapse elimination a stereotypical process and, if so, what is the sequence of molecular events underlying synapse disassembly?
Answers to these questions will not only reveal mechanisms underlying developmental and neurodegenerative disorders, but will also provide insight into the molecular signals involved in synaptic strengthening, a process believed essential for learning and memory.
G.S. Brigidi and S.X. Bamji (2011) “Cadherin-dependent signalling in synapse formation.” Curr. Opin. Neurobiol. Jan 19. [Epub ahead of print]
M. Aiga, J.N. Levinson, E. Yoshida and S.X. Bamji (2011) N-cadherin and neuroligins cooperate to regulate synapse formation in hippocampal cultures. J. Biol. Chem. Jan 7;286(1):851-8.
A. Guo, L. Tapia, S.X. Bamji, M. Cynader and W. Jia. (2010) Progranulin deficiency leads to enhanced cell vulnerability and TDP-43 translocation in primary neuronal cultures. Brain Res. 17;1366:1-8.
J.N. Levinson, R. Li, R. Kang, H. Moukhles, A. El-Husseini and S.X. Bamji (2010). Postsynaptic scaffolding molecules modulate the localization of neuroligins. Neurosci. 165(3):782-793.
TP O’Connor, K Cockburn, W Wang, L Tapia, E Currie, SX Bamji (2009). Semaphorin 5B mediates synapse elimination in hippocampal neurons. Neural Dev. 4:18.
Y Sun, M Aiga, E Yoshida, PO Humbert, and SX Bamji (2009). Scribble interacts with β-catenin to regulate the localization of synaptic vesicles. Mol. Cell Biol. 20(14):3390.
Lee SH, Peng IF, Ng YG, Yanagisawa M, Bamji SX, Elia LP, Balsamo J, Lilien J, Anastasiadis PZ, Ullian EM, Reichardt LF. (2008). Synapses are regulated by the cytoplasmic tyrosine kinase Fer in a pathway mediated by p120catenin, Fer, SHP-2, and beta-catenin. J Cell Biol. 183(5):893-908.
Krivosheya D, Tapia L, Levinson JN, Huang K, Kang Y, Hines R, Ting AK, Craig AM, Mei L, Bamji SX, El-Husseini A. (2008). ErbB4-neuregulin signaling modulates synapse development and dendritic arborization through distinct mechanisms. J Biol Chem. 283(47):32944-56.
S.X. Bamji, B. Rico, N. Kimes, and L.F. Reichardt (2006). BDNF mobilizes synaptic vesicles and regulates synaptic density via modulation of cadherin-β-catenin interactions. J. Cell Biol. 174(2):289-299.
S.X. Bamji (2005) Minireview:- Cadherins: Actin with the cytoskeleton to form synapses. Neuron 47:175-178.
S.X. Bamji, K. Shimazu, N. Kimes, J. Huelsken, W. Birchmeier, B. Lu and L.F. Reichardt. (2003). Role of β-catenin in synaptic vesicle localization and presynaptic assembly. Neuron 40(4):719-731.
A. Gloster, H. El-Bizri, S.X. Bamji, D.H. Rogers, and F.D. Miller. (1999) Early induction of Tα1 α-tubulin transcription in neurons of the developing nervous system. J. Comp. Neurol. 405(1):45-60.
R. Aloyz, S.X. Bamji, C.D. Pozniak, D.R. Kaplan, and F.D. Miller. (1998) P53 is essential for developmental neuron death as regulated by the TrkA and p75 neurotrophin receptors. J. Cell Biol. 143(6):1691-1703.
X.M. Yang, J. Toma, S.X. Bamji, J. Kohn, M. Park and F.D. Miller. (1998) Autocrine regulation of neuronal growth through hepatocyte growth factor and its receptor, the met tyrosine kinase. J. Neurosci. 18:8369-8381.
S.X. Bamji, M.Majdan, C.D. Pozniak, D.J. Belliveau, R. Aloyz, J.Kohn, C.G. Causing and F.D. Miller (1998) The p75 neurotrophin receptor mediates neuronal apoptosis and is essential for naturally-occurring sympathetic neuron death. J. Cell Biol. 140(4):911-923.
J. Fawcett, S.X. Bamji, R. Aloyz, C.G. Causing, T.A. Reader, D.R. Kaplan, R. Murphy, J. McLean and F.D. Miller. (1998) Functional evidence that BDNF is an anterograde neuronal trophic factor in the central nervous system. J. Neurosci. 18(8):2808-2821.
M. Majdan, C. Lachance, A. Gloster, R. Aloyz, C. Zeindler, S.X. Bamji, A. Bhakar, D.J. Belliveau, J.P. Fawcett, F.D. Miller, and P.A. Barker (1997) Transgenic mice expressing the intracellular domain of the p75 neurotrophin receptor undergo neuronal apoptosis. J. Neurosci. 17(18):6988-6998.
C.G. Causing, A.Gloster, R. Aloyz, S.X. Bamji, E. Chang, J. Fawcett, G. Kuchel, and F.D. Miller (1997) Synaptic innervation density is regulated by neuron-derived BDNF. Neuron 18:257-267.
S.X. Bamji and F.D. Miller (1996) Comparison of the expression of a Tα1:nlacZ transgene and Tα1 tubulin mRNA in the mature central nervous system. J. Comp. Neurol. 374:52-69.
F.D. Miller, D. H. Rogers, S.X. Bamji, R.S. Slack, and A.Gloster (1996) Analysis and manipulation of neuronal gene expression using the Tα1 α-tubulin promoter. Seminars in Neurosci. 8:117-124.
S.X. Bamji and I. Orchard (1995) Pharmacological profile of octopamine and 5HT receptors on the lateral oviducts of the cockroach, Periplaneta americana. Arch. Insect Biochem. Physiol. 28:49-62.