Ultrastructure of Synapses in the Mammalian Brain

Abstract

The morphology and molecular composition of synapses provide the structural basis for synaptic function. This article reviews the electron microscopy of excitatory synapses on dendritic spines, using data from rodent hippocampus, cerebral cortex, and cerebellar cortex. Excitatory synapses have a prominent postsynaptic density, in contrast with inhibitory synapses, which have less dense presynaptic or postsynaptic specializations and are usually found on the cell body or proximal dendritic shaft. Immunogold labeling shows that the presynaptic active zone provides a scaffold for key molecules involved in the release of neurotransmitter, whereas the postsynaptic density contains ligand-gated ionic channels, other receptors, and a complex network of signaling molecules. Delineating the structure and molecular organization of these axospinous synapses represents a crucial step toward understanding the mechanisms that underlie synaptic transmission and the dynamic modulation of neurotransmission associated with short-and long-term synaptic plasticity.

Strategies for immunohistochemical protein localization using antibodies: What did we learn from neurotransmitter transporters in glial cells and neurons

“…A plasma membrane is about 5 nm thick and the width of the extracellular space (the distances between neighboring cellular extensions) is typically in the range 20-40 nm, while the diameter of a glutamate transporter trimer is believed to be about 8 nm (Yernool et al, 2004). Cellular elements are tightly intermingled (Kirov et al, 1999;Sorra and Harris, 2000;Witcher et al, 2010;Harris and Weinberg, 2012;Mathiisen et al, 2010). This is schematically illustrated in figure 8.…”

A binding site outside the canonical PDZ domain determines the specific interaction between Shank and SAPAP and their function

“…In addition to orchestrating PSD formation, these scaffold proteins also serve to control the trafficking and clustering of receptors on the plasma membranes and to interface with actin cytoskeletons at synapses (15,18,19). Mutations of DLGs, SAPAP, and Shank have been found to cause or associate with various psychiatric disorders, including autism spectrum disorder (ASD), depression, and schizophrenia (20-28), further supporting the importance of these proteins in normal brain development and functions.Electron and superresolution light microscopy imaging studies (4,5,18,(29)(30)(31)(32) have revealed that proteins in PSDs form distinct layers along the axodendritic axis of synapses with a sequential order of membrane-spanning glutamate receptors and cell adhesion molecules, DLGs, the SAPAP and Shank scaffolds, and actin cytoskeletons. Such a distinct layered structure in PSDs depends critically on the specific interactions between the scaffold proteins.…”

“…Electron and superresolution light microscopy imaging studies (4,5,18,(29)(30)(31)(32) have revealed that proteins in PSDs form distinct layers along the axodendritic axis of synapses with a sequential order of membrane-spanning glutamate receptors and cell adhesion molecules, DLGs, the SAPAP and Shank scaffolds, and actin cytoskeletons. Such a distinct layered structure in PSDs depends critically on the specific interactions between the scaffold proteins.…”

“…Shank | SAPAP | PDZ | synapse | specific interaction P ostsynaptic density (PSD) at excitatory synapses refers to disk-shaped, densely packed mega-protein assemblies located beneath postsynaptic membranes (1)(2)(3)(4)(5). A set of highly abundant scaffold proteins, including DLGs (disc large proteins including PSD-95, PSD-93, and SAP102), SAPAP (synapse-associated protein 90/postsynaptic density-95-associated protein; also known as GKAP or DLGAP), and Shank, are known to be critical for the formation, stability, and neuronal activity-dependent dynamic regulations of PSDs (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17).…”

Calcium Signaling in Dendritic Spines

“…Indeed, many studies have shown that the spine neck provides a significant barrier to diffusion that allows compartmentalization of biochemical and electrical signals in the spine head (Yuste and Denk 1995;Svoboda et al 1996;Grunditz et al 2008;Bloodgood et al 2009). The generalizability of these conclusions to non-mushroom spines (see Harris and Weinberg 2012), such as those with no discernible neck (stubby spines) or those with a long neck and small head (thin spines), is still unclear.…”