Volume transmission and wiring transmission from cellular to molecular networks: history and perspectives

The present paper deals with a fundamental issue in neuroscience: the inter-neuronal communication. The paper gives a brief account of our previous and more recent theoretical contributions to the subject and also reports new recent data that support some aspects of our proposal on two major modes of communication in the central nervous system: the wiring and the volume trasmission. There exist two competing theories on inter-neuronal communication: the neuron doctrine and the theory of the diffuse nerve network, supported by Cajal and Golgi, respectively (see their respective Nobel Lectures). The present paper gives a brief account of a view on inter-neuronal communication in the brain, the Volume and Wiring Transmission, that to a great extent reconcile these two theories. Thus, the theory of Volume and Wiring Transmission is summarised and its recent developments that allow to extend these two modes of communication from the cellular network to the molecular network level is also briefly illustrated. The explanatory value of this broadened view is further enhanced by our recent proposal on the existence of a Global Molecular Network enmeshing the entire central nervous system. It may be interesting to note that also the Global Molecular Network is reminiscent of the old reticular theory of Apathy. Finally, the so-called "tide hypothesis" for diffusion of signals in the brain is briefly discussed and its possible extension to the molecular level is for the first time introduced. One of the early indirect evidence supporting Volume Transmission in the brain was the study on transmitter-receptor mismatches. Thus, as an experimental part of the present work a new approach to evaluate transmitter-receptor mismatch is given and the evidence for an inter-relationships between temperature micro-gradients and mismatch is provided