ReviewToward a molecular catalogue of synapses
Section snippets
Neuron diversity
The development of microscopy and novel cell staining methods during the 19th century led to the all important cell theory and the neuron doctrine (Finger, 1994) (and other papers in this issue). The extraordinary diversity of neuronal architecture revealed by Cajal’s illustrations led to the realisation that the brain comprises a vast array of different neurons, which was in stark contrast to some simpler organs, such as the liver, with a fairly small number of similar shaped cells. This
Developing a synapse signature of molecular markers
The computational functions of the brain are conducted at many ‘anatomical’ levels: brain regions and local circuits, and as mentioned in the previous section, also at the level of dendrites and their branches. It is now well established that the molecular circuitry within synapses plays an important role in computational functions. For example, synaptic plasticity and signalling to the nucleus require particular sets of synaptic proteins. It is therefore necessary to consider the need to
Applications of a synapse catalogue and cataloguing techniques
There are a wide range of applications for a synapse catalogue based on synapse proteome markers. It would be of interest to simply define the diversity of synapses on a given neuron, and then brain region and ultimately the entire brain. One exciting outcome of this investigation might be to ask for humans, which have an estimated 1014-15 synapses: how many types (as defined by their synapse proteome signatures) are there? In line with the earlier discussion on the combinations of protein
Functional significance of different synapse compositions
The levels of expression of individual synapse proteins are critical to the function of the synapse. This is very clearly seen in studies of ∼ 100 mouse knockouts where the reduction of expression of a single synaptic protein leads to changes in synaptic physiology (see G2Cdb database for repository of synaptic physiology phenotypes: www.genes2cognition.org/db). The synapse may be rather sensitive to these changes in levels of expression since heterozygous mice with 50% changes in protein
Concluding comments
We are indebted to Cajal and Golgi for revealing the extraordinary and complex world of neuronal diversity. Molecular techniques in the realm of gene expression and proteomic methods are beginning to follow Cajal’s systematic histological methods with systematic molecular profiling of neurons and synapses. The definition of the molecular expression profile for all neurons and synapses is within reach and will provide a definitive molecular composition of the brain.
Many scientists believe that
Acknowledgments
SG is supported by the Wellcome Trust. Thanks to J. Turner for manuscript preparation.
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