Non-synaptic interaction between neurons in the brain, an analog system: far from Cajal-Sherringtons's galaxy

The functional interactions between neurons without synaptic contacts are specialized to function on a time scale of seconds (minutes) and a distance scale of hundreds of micrometers. These nonsynaptic receptors and transporters are of high affinity, have many implications for psychiatry for understanding e.g. depression, changes in mood, in appetite, affective illnesses etc. It is, therefore, suggested that many drugs applied in psychiatric diseases, exert their effects after diffusion through extracellular spaces and may mimic the mode, or may influence the effect of endogenous ligands. The nonsynaptic chemical communication between neurons, and between neurones and target cells, via both pre- and postsynaptic sites, seems likely to achieve growing recognition. This system has a similar degree of selectivity to that of synaptic circuitry but have, in addition, a domain of versatility and plasticity in "hardwired" circuitry. The brain is a wired instrument, but its neurons, besides cabled information processing (through synapses), are able to talk to each other without synaptic contact. It is suggested, therefore that the nonsynaptic tonic presynaptic modulation of chemical transmission, plays a physiological role in the brain in shaping emotion, behaviour or learning processes, or in controlling the balance between sympathetic and parasympathetic nervous system, or the nonsynaptic released transmitter is able to produce responses of the target cells and a local fine tuning of cytokine production (cf. Elenkov et al., 2000), steroid secretion and possible many other functions not yet discovered. The spatial and temporal effect of transmitters on nonsynaptic receptors located on axon terminals, adopts the strength of transmission to a given situation. This will not only influence the function of the neurons system in health and disease, but also therapeutic and untoward effects of drugs that bind these nonsynaptic receptors and transporters (Vizi, 2000).