The human genome is relatively small and simple compared with the human brain. “Much of it consists of repetitive sequences,” says Thomas C. Südhof, a professor of cellular physiology at Stanford University in California. “We don’t really understand the human genome at this point, and it will be a while before we do.” And according to him, the same is especially true for the human brain.
The Nobel Prize winner briefly introduced the subject at the start of the MDC Lecture: The axons and dendrites of the 1012 neurons in the 1.5-kilogram cerebral organ create vast overlapping networks – networks that are connected by 1019 synapses. These countless junctions, which are formed over a person’s lifetime, organize themselves, perform special functions, and are later eliminated. “Synapses are the fundamental computational unit of the brain,” says Südhof. They do more than just transmit “conversations” between cells; they also change the incoming information. How they precisely do this is still unclear, even for simple networks.
What determines synapse formation?
“We want to understand the molecular logic that guides synapse formation,” says Südhof. “Which of these molecules are central regulators of the molecular logic of synapses and which ones are bystanders?” He provided the some 200 researchers attending his lecture with examples from two families of molecules: the already well-studied neuroligins and the still poorly understood latrophilins.
The individual neuroligins change synapse properties – depending on the type of cell, the location in the neural network, or the region of the brain, precisely defined characteristics develop. “A network needs as many different kinds of synapses as possible in order to process information and continually transform itself,” says Südhof. In experiments, however, latrophilin 2 was a vital part in causing synapses to form. Mice lacking this gene were unable to survive.
A molecular mosaic
Südhof compares his work on synapses to the analysis of a Byzantine mosaic. Each stone has a very specific function in its section. But if you remove individual stones they appear to be nearly identical. All of them are about the same size, even if their shape varies. Their color can be divided into broad groups. “You need some context. It’s not much different with synapses,” says Südhof. If you want to define molecular mechanisms, you can’t ignore the other surrounding molecules. “They cooperate with one another and bind to different ligands, thus triggering a signaling pathway.”
Is this enough to create a coherent picture? No, says Südhof. “But we hope to be able to decipher the logic when we – much like in cancer biology – identify intracellular signaling pathways.”