The first layout of brain organization was provided by studies relying on the abnormalities resulting from lesions of the neuronal tissue, caused either by accidents or by hemorrhages, such as that of the area identified by Paul Broca (1824-1880). The design of the first brain atlas provided a building block in our comprehension of brain

structure, with the definition of the Brodmann areas and the design of the first brain atlas (1909). Progress in the knowledge of the fine structure of the brain was marked by the appearance of detailed anatomies, with the description of neurons and their projections carried out by S. Ramón Y Cajal (1852-1934). In spite of the progress Inhibitors,research,lifescience,medical made possible by the refinement of brain atlases, and then confirmed by functional magnetic resonance imaging (fMRI), our knowledge of brain function and dysfunction is only slowly Inhibitors,research,lifescience,medical progressing. Developments in the understanding the functional properties of neurons and their communications was marked by a series of fundamental steps. The first was the controversy between the Italian physicist Alessandro Volta (1745-1827)

and his compatriot the physician Luigi Galvani (1737-1798), who posited for the first time the existence of “animal electricity.” Proper studies of the electrical properties Inhibitors,research,lifescience,medical of neurons had, however, to await the development of electronics, and it was only in 1952 that Alan Hodgkin and Aldous Huxley established Inhibitors,research,lifescience,medical the theory explaining action potential properties. It was indispensable to understand how neurons, which are the building blocks of our brain, communicate, and how the electrical signal is transmitted from one cell to another. A contribution to Inhibitors,research,lifescience,medical our understanding of neurotransmission was made by the French physiologist Claude Bernard (1813-1878) with his postulate about the existence of a chemical transmitter that relayed the information between the nerve and the muscle. He based his hypothesis on the Pictilisib datasheet observation that transmission of the nerve impulse, which

normally provokes the contraction of the muscle, was blocked by the plant extract tubocurare, while the muscle still responded unless to direct electrical stimulation. Subsequently, Otto Loewi (1873-1961) identified that stimulation of the vagus nerve caused the release of a soluble factor that slowed down the heartbeat. First termed “vagus stoff” this substance was soon identified as acetylcholine, and it was found that this molecule activated the G-coupled muscarinic and the ionotropic nicotinic receptors, such as those expressed at the neuromuscular junction. The work of John Eccles (1903-1997) and Bernard Katz (1911-2003) with Ricardo Miledi provided the necessary steps to finally developing the general principles explaining synaptic transmission.