Ultrastructural features of hippocampal CA1 synapses with respect to synaptic enhancement following repeated PKA activation.

We reported previously that repeated activations, but not a single activation, of cyclic AMP-dependent protein kinase (PKA), led to a slowly developing (requiring approximately 1 week to develop) long-lasting (lasting > or = 3 weeks) enhancement of synaptic transmission efficiency in the organotypic slice culture of the rat hippocampus. It was accompanied by an increase in the number of synapses identified immunohistochemically. To answer the question of whether the "perforated synapse", which is known to occur transiently after the induction of long-term potentiation (LTP) in combination with the enlargement of postsynaptic density (PSD), is involved also in this slow/persistent synaptic enhancement, we examined the ultrastructural changes after the repeated activations of PKA. The answer was partially yes (occurrence of perforated synapses was increased) but partially no (the increase in the number of perforated synapses was not transient but persistent; mean apparent size of PSD did not increase). These results suggest that the mechanism of the slow/persistent synaptogenesis shares limited features with the mechanism of the quick/transient morphogenesis after LTP.