The concept of chemical neurotransmission--variations on the theme

The present concept of chemical neurotransmission occurring purely through synaptic transmission has dominated neurobiological thinking for about the last 40 years. According to this conventional view neurotransmitters are substances that are synthesized within the neurones, liberated into the synaptic cleft after stimulation of the nerve, and that finally elicit a biologically plausible response in the postsynaptic target cell or the nerve terminal itself. This concept undoubtedly comprises the main body of interneuronal chemical signalling. However, a large amount of evidence, obtained during the last two decades, suggests that there are a number of parallel mechanisms, which may essentially participate in neuronal signalling, or at least modulate it. Thus, the recent progress of research has provided the following compelling evidence: 1) a large variety of substances, some of them synthesized in non-neuronal cells, actually participate actively in neuronal signalling; 2) functional connections in brain are not determined by the synaptic connections only; 3) glial cells have an active and fundamental role in signal transmission; and 4) the signalling properties and mechanisms of each neurone are constantly under functional and structural regulation. The aim of this review is to present shortly some of the central concepts and/or mechanisms that have risen during the last two decades. Also the functional and/or clinical relevance of these mechanisms is addressed briefly.