About the Lab
For more than three decades this laboratory has been concerned with understanding how the nervous system’s synapses function, how they develop and how they regenerate after trauma. Such information is essential for a comprehensive understanding of the factors that bring about certain diseases of the nervous system and for developing ways of improving recovery after trauma.
We have done most experiments on vertebrate neuromuscular junctions, particularly those of frog, because they are the best understood of all synapses, but we have also studied neuron-to-neuron synapses in the brains of both vertebrates and invertebrates.
Over the years our experimental approaches have included in vivo microsurgery, tissue culture, light and electron microscopy, immunocytochemistry, protein purification, molecular genetics, in situ hydridization, and electrophysiology.
We are currently using the nascent technology of high-resolution electron microscope tomography to study at 2-3 nm spatial resolution the organization and behavior of macromolecules at synapses. The information that is obtained provides unique insights about the molecular mechanisms involved in synaptic impulse transmission and in synapse formation. To augment these studies we are exploring methods for localizing synaptic proteins characterized by biochemistry to specific macromolecules observed by electron microscope tomography.
We are also developing software, called EM3D, a unified application designed specifically for structural cell biologists that allows a user to proceed from an electron microscope tomography data set of a specimen to a collection of 3D surface models of structures within the specimen. EM3D also includes computational tools that quantify spatial characteristics on a vertex-by-vertex basis upon the surface models. These technologies can be used to examine how macromolecular organization regulates cell function in any tissue.
In addition to being equipped with the standard apparatus used for cellular and molecular neurobiological experiments, the lab operates the Stanford High Resolution Electron Microscope Facility for Biomedical Sciences, which features an FEI Polara electron microscope for tomography and single particle analysis.
Some of the lab’s contributions are:
McMahan, U.J. and S.W. Kuffler. Visual Identification of synaptic boutons on living ganglion cells and of varicosities in post-ganglionic axons in the heart of the frog. Proc. Roy. Soc. Lond. B. 177:485-508, 1971.
McMahan, U.J. and Spitzer, N.C. and Peper, K. Visual identification of nerve terminals in living isolated skeletal muscle. Proc. Roy. Soc. Lond. B. l8l:42l-430, 1972.