Membrane and cytoplasmic structure at synaptic junctions in the mammalian central nervous system.

Application of rapid freezing, freeze substitution fixation, and freeze fracture techniques to the study of synaptic junctions in the mammalian central nervous system has revealed new aspects of synaptic structure that are consistent with and partially explicate advances in synaptic biochemistry and physiology. In the axoplasm adjacent to the presynaptic active zone, synaptic vesicles are linked to large spectrin-like filamentous proteins by shorter proteins that resemble synapsin I in morphology. This mesh of presynaptic filamentous proteins serves to concentrate synaptic vesicles in the vicinity of the active zone. The affinity with which the vesicles are bound by the mesh is probably modulated by the extent of phosphorylation at specific sites on the constituent filamentous proteins, and changes in the binding affinity result in changes in transmitter release. The structural organization of the postsynaptic density in Purkinje cell dendritic spines consists of very fine strands with adherent, heterogeneous globular proteins. Some of these globular proteins probably correspond to protein kinases and their substrates. The postsynaptic density, positioned at the site of the maximal depolarization caused by synaptic currents, apparently serves as a supporting framework for a variety of proteins, which respond to and transduce postsynaptic depolarization. At least two classes of filamentous protein fill the cytoplasm of spines with a complex mesh, which presumably contributes to maintenance of the spine shape. Membrane bound cisterns are a ubiquitous feature of Purkinje cell dendritic spines. Studies of rapidly frozen tissue with electron probe microanalysis and elemental imaging reveal that these cisterns take up and sequester calcium, which is derived from the extracellular space, and which probably enters the spine as part of the synaptic current.