How Nerve Cells Get In Touch - A Molecular Model Of Synapse Formation And Retrograde Signalling In The Brain

Researchers at the Max Planck Institute for Experimental Medicine, Göttingen/Germany, and at the University of Texas Southwestern Medical Center, Dallas/Texas, characterized a novel family of cell surface proteins that may regulate the generation of functional networks between nerve cells in the brain by inducing synapse formation (Proc. Natl. Acad. Sci. USA 96, 1100-1105; Feb. 2, 1999).

Information in the brain is transmitted at synapses which are highly sophisticated contact zones between a sending and a receiving nerve cell. They have a typical asymmetric structure where the sending, presynaptic part is specialized for the secretion of neurotransmitters and other signalling molecules while the receiving, postsynaptic part is composed of a complex signal transduction machinery.

In the developing human embryo, cell recognition mechanisms with high resolution generate an ordered network of some 1015 synapses, linking about 1012 nerve cells. The extraordinary specificity of synaptic connections in the adult brain is generated in five consecutive steps. Initially, immature nerve cells migrate to their final location in the brain (1). There, they form processes, so called axons. Axons grow, often over quite long distances, into the target region that the corresponding nerve cell is supposed to hook up with (2). Once arrived in the target area, an axon selects its target cell from a large number of possible candidates (3). Next, a synapse is formed at the initial site of contact between axon and target cell. For this purpose, specialized proteins are recruited to the synaptic contact zone (4). Newly formed synapses are then stabilized and modulated, depending on their use (5). These processes result in finely tuned networks of nerve cells that mediate all brain functions, ranging from simple movements to complex cognitive or emotional behaviour.

Until very recently, the molecular mechanisms that regulate synapse formation in the developing brain w

Contact: Nils Brose

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