Review: Fine structure of synaptogenesis in the vertebrate central nervous system

Abstract

This article reviews studies of the formation of synaptic junctions in the vertebrate central nervous system. It is focused on electron microscopic investigations of synaptogenesis, although insights from other disciplines are interwoven where appropriate, as are findings from developing peripheral and invertebrate nervous systems. The first part of the review is concerned with the morphological maturation of synapses as described from both qualitative and quantitative perspectives. Next, epigenetic influences on synaptogenesis are examined, and later in the article the concept of epigenesis is integrated with that of hierarchy. It is suggested that the formation of synaptic junctions may take place as an ordered progression of epigenetically modulated events wherein each level of cellular affinity becomes subordinate to the one that follows. The ultimate determination of whether a synapse is maintained, modified or dissolved would be made by the changing molecular fabric of its junctional membranes. In closing, a hypothetical model of synaptogenesis is proposed, and an hierarchial order of events is associated with a speculative synaptogenic sequence. Key elements of this hypothesis are 1) epigenetic factors that facilitate generally appropriate interactions between neurites; 2) independent expression of surface specializations that contain sufficient information for establishing threshold recognition between interacting neurites; 3) exchange of molecular information that biases the course of subsequent junctional differentiation and ultimately results in 4) the stabilization of synaptic junctions into functional connectivity patterns.

Preferential Termination of Corticorubral Axons on Spine-Like Dendritic Protrusions in Developing Cat

“…Identification of synapses. Profiles with parallel membranes at putative presynaptic and postsynaptic terminals and dense material in the synaptic cleft were regarded as synapses if they f urther satisfied one or both of the following criteria (see Vaughn, 1989): (1) synaptic vesicles accumulating at the presynaptic membrane specialization, and (2) postsynaptic membrane specialization and thickening. The presence of synapses was confirmed by observing at least three consecutive sections.…”

“…Approximately 10% of the CR synapses did not exhibit an obvious postsynaptic membrane specialization. It is likely that these represent primordial synapses (Hayes and Roberts, 1973;Hinds and Hinds, 1976;Juraska and Fifkova, 1979;Blue and Parnavelas, 1983;Kunkel et al, 1987;Vaughn, 1989). These synapses were, therefore, included in the analysis, although they did not satisf y the latter criterion.…”

Ontogeny of postsynaptic density proteins at glutamatergic synapses

“…For example, identification of glutamatergic synapses by using glutamate immunolabeling can be problematic (Broman et al, 2000). The earliest stages in synapse structural development may vary (Vaughn, 1989); in hippocampal neurons in vitro, the earliest synaptic contacts lack a distinct PSD and have vesicles of variable forms (Ahmari et al, 2000;Ziv and Garner, 2004). Furthermore, spine synapses, typical of adult glutamatergic synapses in the CA1stratum radiatum, are rare at P2, with most synapses formed directly on dendrite shafts (Fiala et al, 1998;Petralia et al, 2003); physiological studies confirm that functional glutamatergic synapses form directly on dendrite shafts of CA1 pyramidal neurons at P2 (Durand et al, 1996).…”

Normal formation of the postsynaptic elements of GABAergic synapses in the reeler cerebellum

“…To establish efficient GABAergic synaptic transmission, it is crucial that both preand post-synaptic elements mature [3,16,39,64]. Maturation of postsynaptic elements requires that GABA A receptor subunit-genes are expressed, the subunit-proteins are trafficked and the receptors are clustered at appropriate places adjacent to the GABA-releasing sites.…”

“…For efficient GABAergic synaptic transmission, it is crucial that GABA A receptors are targeted to and clustered at an appropriate synaptic site opposite the GABA-releasing site [3,16,39,64]. In the cerebellum, granule cells express the GABA A receptor α1 and α6 subunit mRNAs and the subunit proteins are targeted to the GABAergic synaptic site in the synaptic glomeruli [28,47,69].…”