Volume Transmission and the Russian-Doll Organization of Brain Cell Networks

The central nervous system (CNS) has been proposed to be formed by functional modules (FMs) that are structurally organized as “Russian dolls”, which form transient assemblies, according to the different integrative tasks that networks within the CNS have to carry out. Integration is achieved by means of communication processes among and within FMs. Two major types of communication processes occur in the CNS, wiring transmission (WT) and volume transmission (VT). WT involves classical synaptic transmission via diffusion of a neurotransmitter across the synaptic cleft, while VT is transmission via a neuroactive substance that is carried by the extracellular and cerebrospinal fluids to distant targets. Recently, evidence has been obtained for the existence of tunneling nanotubes that mediate WT and microvesicles that mediate VT, allowing horizontal transfer of receptors, RNAs, and micro-RNAs. The recognition and decoding process at the target level involves receptor heteromers (receptor mosaics) that are generated by direct receptor–receptor interactions, as an emergent property of this system. Receptor mosaics allow the integration of incoming information at the plasma membrane level. These new aspects of the structural and functional organization of the CNS open up a new field of investigation in the physiology and pathology of the CNS.