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During the past decade, there has been a fundamental change in our understanding of biochemical signalling pathways. Traditionally, signalling cascades were studied in isolation, but it now seems that their effects emerge from interactions between many biochemical pathways. As Mary Kennedy and colleagues discuss in a Review article on page 423 of this issue, this view has transformed our thinking about synaptic plasticity.

Memory storage in the brain depends on alterations in the strength of excitatory synapses. These changes are regulated by many biochemical signalling pathways in postsynaptic spines. Kennedy and colleagues highlight the integrated function of five signalling cascades that control physiological processes that are crucial for synaptic plasticity and/or neuronal homeostasis: regulation of AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors, polymerization of the actin cytoskeleton, local protein synthesis, gene expression and neuronal apoptosis. The roles of the small GTPases Ras, Rap and Rac in biochemical signalling are highlighted, as recent discoveries have shown their significance in the integration of different pathways in synaptic plasticity. The authors also consider the importance of the intracellular localization of signalling molecules through the action of scaffold proteins.

This Review article is accompanied by a poster that depicts the key signalling cascades that influence postsynaptic functions in the spine. This is intended as a starting point from which to refine our understanding of the integration of these pathways in synaptic plasticity. The poster, which has been produced with generous financial support from Sigma-RBI, a division of Sigma-Aldrich, will be freely available online until the end of November 2005 (

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In This Issue. Nat Rev Neurosci 6, 415 (2005).

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