Synaptic plasticity and perforated synapses: their relevance for an understanding of abnormal synaptic organization

Perforated synapses refer to a synaptic type found in the central nervous system, and characterized by a discontinuous postsynaptic density when viewed in transverse sections; they are doughnut-shaped or horseshoe-shaped when viewed in en face views. They are large, and are considered to represent single synapses. In this review the evidence for their being intermediates in synaptic turnover is examined. In particular, the view that they originate from conventional, non-perforated synapses, enlarge, and subsequently split to give rise to a new generation of non-perforated synapses, is critically assessed. It is concluded that all the necessary stages in such a scheme have not been unequivocally demonstrated, and an alternative is considered. According to this, perforated and non-perforated synapses constitute separate populations from early in their development, each representing complementary forms of synaptic plasticity. It is further argued that the perforated synapse population can be subdivided into synapses with simple, discrete perforations, those with re-entrant zones, and those with a more complex fragmented form of organization. There is evidence that it is synapses of the latter type that are implicated in synaptic plasticity. An attempt is also made to discover whether the results of synaptic studies on both the normal ageing human brain and the brain in Alzheimer's disease, throw light on the role of perforated synapses in synaptic plasticity. It is suggested that there may be a loss of perforated synapses in Alzheimer's disease, although definitive data are required to test this possibility.