Exploring the synaptome: promising new technologies

de Felipe, J.

The principal goal in neuroanatomy is to define the detailed structural design of the nervous system. This challenge is one of the first steps towards understanding how neural circuits contribute to the functional organization of the nervous system, both in health and disease. The main difficulties involve unraveling the extraordinary complexity of the nervous system and to define how information flows through this finely organized synaptic network. Over the years, neuroanatomy has evolved considerably thanks to the use of classical techniques and the introduction of new procedures. The term ?connectome? has recently been proposed to refer to the highly organized connection matrix of the human brain, in analogy to the human genome. However, defining how information flows through such a complex system represents so difficult a task that it would seem unlikely it could be achieved in the near future, or, for the most pessimistic, perhaps never. Circuit diagrams of the nervous system can be considered at different levels, although they are surely impossible to complete at the synaptic level. Even for a small mammal like the mouse it is impossible to fully reconstruct the brain at this level (we would need over 1.4 x 109 sections to fully reconstruct just one mm3 of tissue). Therefore, complete reconstructions of a small region of the mammalian brain are feasible, while structures like the cerebral cortex cannot be fully reconstructed. Despite the technical difficulties, by adopting appropriate strategies with the tools now available coupled with the development of huge international projects, it should be possible to make spectacular advances in unraveling brain organization, even in humans. Indeed, advances in our capacity to marry macro- and microscopic data may help establish a realistic statistical model that could describe connectivity at the ultrastructural level, the ?synaptome?, giving us cause for optimism.