One century of progress in neuroscience founded on Golgi and Cajal's outstanding experimental and theoretical contributions

Since the discovery and mapping of the neuronal circuits of the brain by Golgi and Cajal neuroscientists have clearly spelled the fundamental questions which should be answered to delineate the arena for a scientific understanding of brain function:• How neurons communicate with each other in a network?• Is there some basic principle according to which brain networks are organised?• Is it possible to map out brain regions specialised in carrying out some specific task?As far as the first point is concerned it is well known that Golgi and Cajal had opposite views on the interneuronal communication. Golgi suggested protoplasmic continuity and/or electrotonic spreading of currents between neurons. Cajal proposed the so-called “neuron doctrine”, which maintained that neurons could communicate only via a specialised region of contiguity, namely the synapse.The present paper has the first and second points as main topics and last century progresses in these fields are viewed as developments of Golgi and Cajal's findings and above all, hypotheses. Thus, we will briefly discuss these topics moving from the transmitter based mapping, which brought neurochemistry into the Golgi–Cajal mapping of the brain with silver impregnation techniques. The mapping of transmitter-identified neurons in the brain represents one of the major foundations for neuropsychopharmacology and a reference frame for the biochemical and behavioural investigations of brain function. Biochemical techniques allowed giving evidence for multiple transmission lines in synapses interacting via receptor–receptor interactions postulated to be based on supramolecular aggregates, called receptor mosaics. Immunocytochemical and autoradiographic mapping techniques allowed the discovery of extra-synaptic receptors and of transmitter–receptor mismatches leading to the introduction of the volume transmission concept by Agnati–Fuxe teams. The Volume Transmission theory proposed the existence of a three-dimensional diffusion of e.g. transmitter and ion signals, released by any type of cell, in the extra-cellular space and the cerebrospinal fluid of the brain. Thus, a synthesis between Golgi and Cajal's views became possible, by considering two main modes of intercellular communication: volume transmission (VT) and wiring transmission (WT) (a prototype of the latter one is synaptic transmission) and two types of networks (cellular and molecular networks) in the central nervous system. This was the basis for the suggestion of two fundamental principles in brain morphological and functional organisation, the miniaturisation and hierarchic organisation.Finally, moving from Apathy's work, a new model of brain networks has recently been proposed. In fact, it has been proposed that a network of fibrils enmeshes the entire CNS forming a global molecular network (GMN) superimposed on the cellular networks.