12/21/2010 PERMALINK
Scientists directly observe synapse validation for the first time in living brain circuits. Newly published research led by Professor Z. Josh Huang, Ph.D., of Cold Spring Harbor Laboratory (CSHL) sheds important new light on how neurons in the developing brain make connections with one another. This activity, called synapse validation, is at the heart of the process by which neural circuits self-assemble, and is directly implicated in pathology that gives rise to devastating neurodevelopmental disorders including autism and schizophrenia. They focused on a particular type of inhibitory neurons, called GABAergic because they communicate via neurotransmitters called GABA (gamma-aminobutyric acid). Some have proposed that nerve cells secrete some kind of repulsive or attractive molecules. "But when you are in the cortex," says Professor Huang. "The distance between different potential partners is so minute—it's inconceivable that kind of mechanism could work. It's more plausible that the cortical neuron's strategy is to initiate synapse formation with almost any nearby target and then to test it, by trying to communicate using synaptic transmission. Most of these tentative connections don't prove to be correct and will be eliminated. Only those between functionally compatible neurons will be validated and strengthened." Huang and and graduate student Yu Fu observed in live cortical circuits precisely how cellular 'glues' in the form of cell-adhesion molecules called neurexins and neuroligins help to make a preliminary connection. "They work like a zipper: two neurons—called pre-synaptic and post-synaptic—are touching; there are adhesion molecules coming from both sides, and they actually lock."