Activity-Dependent Spine Growth

This research article explains that the purpose of the experiment was to investigate the pathways that mediate activity-dependent spine growth and trafficking of postsynaptic density proteins. In this experiment, each spine observed contained a postsynaptic density (PSD) associated with a single excitatory synapse. Large spines hold larger PSDs that contain higher amounts of AMPA-type glutamate receptor (AMPARs) and high-release probability presynaptic terminals with a more active zone area. The PSD-95/SAP90 is highly abundant in postsynaptic density, which can regulate many aspects of synaptic transmission, structure, and function.

The researchers make a very significant observation in stating that the PSD-95 is positioned to link and coordinate multiple pathways regulating synapse structure and function, such as those that control activity-dependent spine growth and protein trafficking. These findings suggest that PSD-95 is required for the transient and activity-dependent spine growth. As a result, PSD-95 is rapidly trafficked out of the dendritic spines in response to the activity, which depends on the calcium/calmodulin-dependent protein kinases (CaMKs) and the regulation of the PSD-95 serine 73 (S73) site. By phosphorylating this site, it indicates that both long-term potentiation (LTP) and LTP-associated spine growth are inhibited; long-term potentiation is accompanied by dendritic spine growth and changes in the composition of the PSD. Furthermore, the phosphorylation of this site demonstrated that CAMKII and PSD-95 triggers first and then terminates the growth process. Therefore, it controls the trafficking of PSD proteins to regulate the assembly of protein complexes needed to promote and sustain synaptic plasticity.

Nevertheless, activity of CaMKII is required for the persistent phase of LTP-associated spine growth. A mutation of PSD-95 at the serine 73 sites was observed to investigate whether the direct regulation of PSD-95 by CaMK controls the activity-dependent of spine growth. As a result, spines of neurons expressing the mutation, S73D PSD-95, had reduced rapid and persistent growth significantly. These findings suggested that phosphorylation of PSD-95 specifically at the CaMKII site limits it rather than enhancing activity-dependent spine growth.

Overall, the research conducted in this article found that spine growth induced by LTP induction requires signaling via PSD-95 and trafficking of SHANK2; this allows the transient removal of PSD-95 and SHANK2, which is regulated during activity-dependent spine growth from active sites. Their findings suggested that the PSD-95 has multiple functions such as regulation of basal synaptic transmission, morphological plasticity, and induction functional plasticity just to name a few. Lastly, the authors were able to conclude that PSD-95 and CaMKII act at multiple steps during plasticity induction in order to trigger and terminate spine growth by trafficking growth promoting