Snare Proteins as Molecular Masters of Interneuronal Communication

In the beginning of the 20 th century the groundbreaking work of Ramon y Cajal firmly established the neuron doctrine, according to which neurons are the basic structural and functional units of the nervous system (1,2). Von Weldeyer coined the term " neuron " in 1891 (3), but the huge leap forward in neuroscience was due to Cajal's meticulous microscopic observations of brain sections stained with an improved version of Golgi's la reazione nera (black reaction). The latter improvement of Golgi's technique made it possible to visualize the arborizations of single neurons that were " colored brownish black even to their finest branchlets, standing out with unsurpassable clarity upon a transparent yellow background. All was sharp as a sketch with Chinese ink " (4). The high quality of both the visualization of individual nerve cells and the work performed on studying the anatomy of the central nervous system lead Ramon y Cajal to the conclusion that ax-ons output the nervous impulses to the dendrites or the soma of other target neurons. The name " dendrite " was coined by His in 1889 (5) and " axon " by von Kölliker in 1896 (6), but it was Ramon y Cajal who developed and provided extensive anatomical evidence for the idea that neurons are dynamically polarized and within each neuron the transmission of information is from the dendrites towards the axon (2). Based upon numerous observations, Ramon y Cajal concluded that neurons are indeed individual cells, which should transmit information between each other at the places of contact and that neuronal somata do not only have trophic function but also participate in the conduction of the neuronal impulses. Further, he argued that the exclusion of substantial continuity between cell and cell leaves open the hypothesis that the nervous impulse is transmitted by contact, as in the articula-tions of electrical conductors, or by a kind of induction, as with induction coils (4). The 1906 Nobel Prize in Physiology or Medicine was awarded jointly to Ramon y Cajal and Camillo Golgi for the development of the silver nitrate im-pregnation technique (2,7). Surprisingly, Golgi still believing that the nervous system was a reticulum, or a connected meshwork, rather than a system made up of discrete cells, delivered his acceptance speech as a sustained attack on the neuron doctrine (7).