Structural Plasticity within the Postsynaptic Density

Abstract

The postsynaptic density (PSD) is a large protein complex that clusters neurotransmitter receptors at the synapse and organizes the intracellular signaling molecules responsible for altering the efficiency of synaptic transmission – termed synaptic plasticity. We propose that synapses from different parts of the brain place unique demands on the process of synaptic transmission and that the structure and composition of the PSD play a role in providing these distinctive properties. To begin to address this question, PSDs were isolated from adult rat cerebella, hippocampi and cortices, three brain areas amenable to straightforward isolation that contain unique distributions of neuronal cell types. Electron-tomography (ET) was used to visualize the fine morphology of the isolated PSDs and calculate total protein occupancy within the PSD structure. Immunogold labeling was utilized to quantify protein composition and distribution of key signaling and scaffold molecules. Although the mean surface area did not significantly differ between PSD types, the PSD thickness, as measured from Cryo ET reconstructions, differed significantly between PSD types. Labeling densities for PSD-95 and αCaMKII were found to differ dramatically among the PSD types, while all regions had moderate to high labeling for βCaMKII, illustrating the importance of βCaMKII to the PSD structure. PSD-95, a scaffold protein, was absent from a fraction of cerebellar PSDs, unlike hippocampal and cortical PSDs, showing that protein composition varies between PSD types. Ripley's K function analysis of immunogold labeled PSDs showed that PSD-95 was clustered in cerebellar PSDs, unlike other PSD types, suggesting a different function for PSD-95 in cerebellar PSDs. In contrast, βCaMKII was found to have similar non-random organization in all PSD types. These results support the idea that the composition and structure of the PSD are modified to achieve the specific synaptic functions required of each brain region.