Wiring and volume transmission in the central nervous system: The concept of closed and open synapses

During the past two decades, several revisions of the concepts underlying interneuronal communication in the central nervous system (CNS) have been advanced. Our group has proposed to classify intercellular communication in the CNS under two general frames: ‘wiring’ (WT) and ‘volume’ transmission (VT). WT is characterized by a single ‘transmission channel’ made by cellular (neuronal or glial) structures and with a region of discontinuity not larger than a synaptic cleft. VT is characterized by the diffusion from a cell source (neuronal or glial) of chemical and electrical signals in the extracellular fluid (ECF) for a distance larger than the synaptic cleft. Based on morphological and functional characteristics, and in light of the distinction proposed, six main modes of intercellular communication can be recognized in the CNS: gap-junction, membrane juxtaposition, and closed synapse (which represent WT-type modes of communication); open synapse, paracrine transmission and endocrine-like transmission (which represent VT-type modes of communication). Closed and open synapses are distinguished on the basis of the sealing of the signal within or the leakage of the signal outside the synapse. Intra-synaptic restriction or extra-synaptic diffusion of transmitters are insured by a number of anatomical arrangements (e.g. glial ensheathment of synapse, size of the synaptic cleft) and functional mechanisms (e.g. density and location of transmitter re-uptake sites and metabolic enzymes). Some central synapses can switch from closed to open state and vice versa, e.g. by changing the amount of transmitter released. Finally, a synapse containing several transmitters can work as an open synapse for one transmitter and as a closed synapse for another.