Kolodkin, a professor in the neuroscience department at Johns Hopkins and a Howard Hughes Medical Institute investigator, discovered and cloned the first semaphorin gene in the grasshopper when he was a postdoctoral fellow. Over the past 15 years, numerous animal models, including strains of genetically engineered mice, have been created to study this family of molecules.
Using two lines of mice one missing semaphorin and another missing neuropilin, its receptor postdoctoral fellow Tracy Tran used a classic staining method called the Golgi technique to look at the anatomy of nerve cells from mouse brains. (The Golgi technique involves soaking nerve tissue in silver chromate to make cells' inner structures visible under the light microscope; it allowed neuroanatomists in 1891 to determine that the nervous system is interconnected by discrete cells called neurons.)
Tran saw unusually pronounced "spines" sprouting willy-nilly in peculiar places and in greater numbers on the dendrites in the neurons of semaphorin-lacking and neuropilin-lacking mice compared to the normal wild-type animals. It's at the tips of these specialized spines that a lot of synapses occur and neuron-to-neuron communication happens, so Tran suspected there might be more synapses and more electrical activity in the neurons of the mutant mice.
The researchers tested this hypothesis by examining even thinner brain slices under an electron microscope.
The spines of both semaphorin-lacking and neuropilin-lacking mice were dramatically enlarged, compared to those of the smaller, spherical-looking spines in the wild-type mice. In wild types, Tran generally noted a single site of connection per spine. In the mutants, the site of connection between two neurons was often split.
Next, the team recorded the electrical output of mutant and wild-type neurons and found that the mutants, with more spines and larg
|Contact: Maryalice Yakutchik|
Johns Hopkins Medical Institutions