Elsevier

Brain Research Reviews

Volume 55, Issue 2, October 2007, Pages 445-449
Brain Research Reviews

Review
Toward a molecular catalogue of synapses

https://doi.org/10.1016/j.brainresrev.2007.05.003Get rights and content

Abstract

1906 was a landmark year in the history of the study of the nervous system, most notably for the first ‘neuroscience’ Nobel prize given to the anatomists Ramon Y Cajal and Camillo Golgi. 1906 is less well known for another event, also of great significance for neuroscience, namely the publication of Charles Sherrington’s book ‘The Integrative Action of the Nervous system’. It was Cajal and Golgi who debated the anatomical evidence for the synapse and it was Sherrington who laid its foundation in electrophysiological function. In tribute to these pioneers in synaptic biology, this article will address the issue of synapse diversity from the molecular point of view. In particular I will reflect upon efforts to obtain a complete molecular characterisation of the synapse and the unexpectedly high degree of molecular complexity found within it. A case will be made for developing approaches that can be used to generate a general catalogue of synapse types based on molecular markers, which should have wide application.

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.

References (41)

  • D. Cheng et al.

    Mol. Cell. Proteomics

    (2006)
  • M.O. Collins et al.

    J. Biol. Chem.

    (2005)
  • K.M. Harris

    Curr. Opin. Neurobiol.

    (1999)
  • A. Inoue et al.

    Curr. Opin. Neurobiol.

    (2003)
  • B.A. Jordan et al.

    Mol. Cell. Proteomics

    (2004)
  • K.W. Li et al.

    J. Biol. Chem.

    (2004)
  • S Okabe

    Mol. Cell. Neurosci.

    (2007)
  • J. Peng et al.

    J. Biol. Chem.

    (2004)
  • M. Sheng et al.

    Neuron

    (1992)
  • S.M. Sunkin

    Trends Genet.

    (2006)
  • S. Takamori et al.

    Cell

    (2006)
  • C.N. Anderson et al.

    J. Physiol.

    (2006)
  • X. Chen et al.

    Proc. Natl. Acad. Sci. U. S. A.

    (2005)
  • J.T. Davie et al.

    Natl. Protoc.

    (2006)
  • W. Denk et al.

    PLoS Biol.

    (2004)
  • T. Ebihara et al.

    J. Neurosci.

    (2003)
  • M.D. Ehlers

    Nat. Neurosci.

    (2003)
  • S. Finger

    Origins of Neuroscience: A History of Explorations into Brain Function

    (1994)
  • S. Gong et al.

    Nature

    (2003)
  • S.G. Grant

    Biochem. Soc. Trans.

    (2006)
  • Cited by (0)

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