The present concept of chemical neurotransmission occurring purely thr
ough synaptic transmission has dominated neurobiological. thinking for
about the last 40 years. According to this conventional view neurotra
nsmitters are substances that are synthesized within the neurones, lib
erated into the synaptic cleft after stimulation of the nerve, and tha
t finally elicit a biologically plausible response in the postsynaptic
target cell or the nerve terminal itself. This concept undoubtedly co
mprises the main body of interneuronal chemical signalling. However, a
large amount of evidence, obtained during the last two decades, sugge
sts that there are a number of parallel mechanisms, which may essentia
lly 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 signa
lling; 2) functional connections in brain are not determined by the sy
naptic connections only; 3) glial cells have an active and fundamental
role in signal transmission; and 4) the signalling properties and mec
hanisms 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 mecha
nisms is addressed briefly.