Neurons are cells which are specialized to communicate with one another, and the language used by nervous systems for this communication is electrochemistry.
The action potentials, or electrical signals, generated by nerve cells and propagated along their axons cannot cross the synapse at the junction between neurons. The electrical signal is therefore converted to a chemical one, which diffuses across the synaptic cleft and initiates electrical signals in the cell on the other side of the cleft.
When an action potential reaches a nerve terminal, it triggers the release of neurochemical transmitters into the synaptic cleft. Transmitter molecules are stored in synaptic vesicles and their release is quantized, with each vesicle containing approximately 10,000 molecules.
Neurotransmitters are released from synaptic vesicles in a process called exocytosis. The arrival of an action potential at a nerve terminal causes vesicles to fuse with the presynaptic membrane and release their contents into the cleft.
That vesicles fuse with the presynaptic membrane can be demonstrated by measuring the capacitance of a neuron, or its ability to store electrical charge. Using microelectrodes, one can show that the capacitance of a neuron increases during neurotransmission. This is consistent with fusion of the vesicles with the cell membrane, which increases in surface area as a result and, therefore, is able to store more electrical charge.
Once the transmitter molecules have acted upon the postsynaptic receptors, they are taken up by the cell which released them and then re-packaged into vesicles. Vesicle recycling ensures that neurotransmitters are always present at nerve terminals. At one end of the cell, vesicles fuse with the membrane to release their contents into the synapes. At the other end, new vesicles are formed from cell membrane materials and then transported to the nerve terminal and filled with transmitter molecules.
Dozens of proteins are known to be involved in synaptic transmission. One such protein is dynamin, which is involved in vesicle formation. During their formation, vesicles are attached to the membrane from which they are made by a 'neck'. Dynamin forms a helix around the neck of nascent vesicles. Extension of the dynamin helix causes the vesicle to break away from the membrane, so that it can be transported to the nerve terminal.
Victor Angonno, a PhD student at the Children's Medical Research Institute in Australia, has shown that a protein called syndapin is essential for dynamin function. The role of syndapin in neurons is not known, but Angonno's work shows that blocking the syndapin-dynamin interaction prevents the formation of new synaptic vesicles, causing neurotransmission to breakdown completely.
The findings have important implications in a number of areas. Conditions such as epilepsy, for example, are characterized by excessive electrical activity in the brain, and the making and breaking of memories is dependent upon alterations in the strength of synaptic connections.
"Syndapin [is] a very specific target for medicines that could treat conditions where there is an overload of nerve activity," says Dr. Phil Robinson, who led the research. "A discovery like this will be vital for future research into many neurological disorders, such as epilepsy, conditions of memory loss and schizophrenia."