Morphogenesis in memory formation: synaptic and cellular mechanisms.

Abstract

We review some of the evidence for structural changes in synapses in response to environmental stimulation. These include changes in synapse number, in distribution of presynaptic vesicles, in synaptic bouton size, and complex changes in the shape and size of synaptic contact zones. Increased numbers of postsynaptic polyribosomal aggregates (PRA) are correlated histologically with developmental plasticity. We discuss the role that dendritically targeted mRNAs and polyribosomes might play in providing rapid, localized synthesis of proteins necessary for structural change. Using synaptoneurosomes, we have demonstrated that depolarization leads to a rapid (1-2 min) increase in PRA and in [35S]methionine incorporation into polypeptides. We have shown that this process is initiated by metabotropic glutamate receptors, which trigger phosphatidyl inositol hydrolysis, leading to release of internal Ca2+ stores and activation of protein kinase C. Entry of external Ca2+, however, seems to downregulate polyribosomal aggregation, via a calmodulin-dependent mechanism, suggesting that translation may be controlled by interaction of ionotropic receptors, voltage-dependent calcium channels, and metabotropic receptors.